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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
New Tools for Monitoring Multiple Myeloma
Advances in drugs and combinations have revolutionized the landscape in multiple myeloma, thus allowing patients to live much longer, according to Bruno Paiva, PhD, director of flow cytometry and the myeloma laboratory at the University of Navarra Clinic in Pamplona, Spain.
“Much better treatment responses are achieved, with long-term remission, so tools are needed for long-term monitoring. The starting point for monitoring is the monoclonal protein secreted by the myeloma tumor cell, which can be measured in serum and urine. Complete remission is defined when that monoclonal component is not detected with routine laboratory techniques, such as immunofixation,” said Dr. Paiva.
Even if the patient may be in complete remission, minimal residual disease is sometimes detected as myeloma can infiltrate the bone marrow. Techniques for identifying minimal residual disease, like cytometry or next-generation sequencing, can detect bone marrow blood aspirate. “The detection of this minimal residual disease corresponds with a significant reduction in survival,” Dr. Paiva warned.
In addition to these techniques, PET-CT is also used. This imaging tool is “very useful for seeing disease both inside and outside the marrow,” said Dr. Paiva.
“As for the future, the FDA [Food and Drug Administration] has just approved the use of minimal residual disease as one of the trial objectives. This may allow drugs to reach patients much sooner, instead of waiting for survival data, which takes much longer to obtain,” he said.
Researchers are also learning how to use minimal residual disease and these imaging techniques to individualize the treatment of patients with myeloma. “Furthermore, since some of these techniques are invasive, such as bone marrow ones, we are trying to focus on peripheral blood. This way, monitoring is minimally invasive, much more comfortable for the patient, and more informative because it can be done many times,” said Dr. Paiva.
Dr. Paiva is extending these imaging techniques “to different scenarios, such as the precursor stages of the disease. Our laboratory is especially known for flow cytometry, and we are launching the NoMoreMGUS project, the largest ever conducted in Spain (and perhaps in Europe) on monoclonal gammopathy of undetermined significance. This is a condition that precedes myeloma. We are looking to study 5000 patients in Spain once a year for 5 years, which means analyzing 25,000 samples.
“On the other hand,” he continued, “we are taking some of these developments to other neoplasms, such as acute lymphoblastic leukemia. And we are interested in using all the potential of cytometry not only to measure tumor cells but also to characterize the immune system as another important biomarker in the pathogenesis of the disease. And, for example, to predict infections, which is very important in patients with myeloma.”
This story was translated from El Médico Interactivo, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
Advances in drugs and combinations have revolutionized the landscape in multiple myeloma, thus allowing patients to live much longer, according to Bruno Paiva, PhD, director of flow cytometry and the myeloma laboratory at the University of Navarra Clinic in Pamplona, Spain.
“Much better treatment responses are achieved, with long-term remission, so tools are needed for long-term monitoring. The starting point for monitoring is the monoclonal protein secreted by the myeloma tumor cell, which can be measured in serum and urine. Complete remission is defined when that monoclonal component is not detected with routine laboratory techniques, such as immunofixation,” said Dr. Paiva.
Even if the patient may be in complete remission, minimal residual disease is sometimes detected as myeloma can infiltrate the bone marrow. Techniques for identifying minimal residual disease, like cytometry or next-generation sequencing, can detect bone marrow blood aspirate. “The detection of this minimal residual disease corresponds with a significant reduction in survival,” Dr. Paiva warned.
In addition to these techniques, PET-CT is also used. This imaging tool is “very useful for seeing disease both inside and outside the marrow,” said Dr. Paiva.
“As for the future, the FDA [Food and Drug Administration] has just approved the use of minimal residual disease as one of the trial objectives. This may allow drugs to reach patients much sooner, instead of waiting for survival data, which takes much longer to obtain,” he said.
Researchers are also learning how to use minimal residual disease and these imaging techniques to individualize the treatment of patients with myeloma. “Furthermore, since some of these techniques are invasive, such as bone marrow ones, we are trying to focus on peripheral blood. This way, monitoring is minimally invasive, much more comfortable for the patient, and more informative because it can be done many times,” said Dr. Paiva.
Dr. Paiva is extending these imaging techniques “to different scenarios, such as the precursor stages of the disease. Our laboratory is especially known for flow cytometry, and we are launching the NoMoreMGUS project, the largest ever conducted in Spain (and perhaps in Europe) on monoclonal gammopathy of undetermined significance. This is a condition that precedes myeloma. We are looking to study 5000 patients in Spain once a year for 5 years, which means analyzing 25,000 samples.
“On the other hand,” he continued, “we are taking some of these developments to other neoplasms, such as acute lymphoblastic leukemia. And we are interested in using all the potential of cytometry not only to measure tumor cells but also to characterize the immune system as another important biomarker in the pathogenesis of the disease. And, for example, to predict infections, which is very important in patients with myeloma.”
This story was translated from El Médico Interactivo, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
Advances in drugs and combinations have revolutionized the landscape in multiple myeloma, thus allowing patients to live much longer, according to Bruno Paiva, PhD, director of flow cytometry and the myeloma laboratory at the University of Navarra Clinic in Pamplona, Spain.
“Much better treatment responses are achieved, with long-term remission, so tools are needed for long-term monitoring. The starting point for monitoring is the monoclonal protein secreted by the myeloma tumor cell, which can be measured in serum and urine. Complete remission is defined when that monoclonal component is not detected with routine laboratory techniques, such as immunofixation,” said Dr. Paiva.
Even if the patient may be in complete remission, minimal residual disease is sometimes detected as myeloma can infiltrate the bone marrow. Techniques for identifying minimal residual disease, like cytometry or next-generation sequencing, can detect bone marrow blood aspirate. “The detection of this minimal residual disease corresponds with a significant reduction in survival,” Dr. Paiva warned.
In addition to these techniques, PET-CT is also used. This imaging tool is “very useful for seeing disease both inside and outside the marrow,” said Dr. Paiva.
“As for the future, the FDA [Food and Drug Administration] has just approved the use of minimal residual disease as one of the trial objectives. This may allow drugs to reach patients much sooner, instead of waiting for survival data, which takes much longer to obtain,” he said.
Researchers are also learning how to use minimal residual disease and these imaging techniques to individualize the treatment of patients with myeloma. “Furthermore, since some of these techniques are invasive, such as bone marrow ones, we are trying to focus on peripheral blood. This way, monitoring is minimally invasive, much more comfortable for the patient, and more informative because it can be done many times,” said Dr. Paiva.
Dr. Paiva is extending these imaging techniques “to different scenarios, such as the precursor stages of the disease. Our laboratory is especially known for flow cytometry, and we are launching the NoMoreMGUS project, the largest ever conducted in Spain (and perhaps in Europe) on monoclonal gammopathy of undetermined significance. This is a condition that precedes myeloma. We are looking to study 5000 patients in Spain once a year for 5 years, which means analyzing 25,000 samples.
“On the other hand,” he continued, “we are taking some of these developments to other neoplasms, such as acute lymphoblastic leukemia. And we are interested in using all the potential of cytometry not only to measure tumor cells but also to characterize the immune system as another important biomarker in the pathogenesis of the disease. And, for example, to predict infections, which is very important in patients with myeloma.”
This story was translated from El Médico Interactivo, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
Survey Highlights Real-World Use of Upadacitinib in Adults With Atopic Dermatitis
, while 7.8% rated their itch as minimally improved.
Also, 27.5% reported itch improvement within one day of taking upadacitinib (Rinvoq), an oral Janus kinase inhibitor that was approved to treat moderate to severe AD in adults and children aged ≥ 12 years in January 2022.
“We have a lot of data about upadacitinib from clinical trials, but sometimes there’s a concern that when you start using a medication in the real world, the effectiveness doesn’t match up with the efficacy observed in clinical trials,” the study’s first author, Jonathan I. Silverberg, MD, PhD, professor of dermatology at George Washington University, Washington, said in an interview after the Revolutionizing Atopic Dermatitis conference, where the study was presented during a late-breaking abstract session. “We always want to confirm or reaffirm clinical trial results with real-world data.”
In SCALE-UP, 6191 adults with moderate to severe AD participating in the patient support program for upadacitinib in the United States were invited to complete a one-time online survey about their experience with upadacitinib, including the degree of and time to itch improvement and skin clearance. The researchers reported on 204 patients who completed the survey questions, for a response rate of 3.3%. The mean age of respondents was 45.3 years, their mean age when diagnosed with AD was 30.3 years; 70.1% were women, and 37% were using topical corticosteroids. In addition, 68.6% were White individuals, 12.3% were Black individuals, 8.8% were Asian individuals or Pacific Islanders, and 0.5% were Native Americans/Alaska Natives.
Duration of upadacitinib treatment was 2-6 months for 50.5% of the patients and 7-12 months for the remaining patients. Starting upadacitinib dose was 15 mg for about 95% of patients and 30 mg for nearly 4% of patients. At the time of the survey, 79.4% of patients were receiving upadacitinib 15 mg once a day, and 19.6% were receiving upadacitinib 30 mg once a day.
Improvements in Itch, Skin Clearance
Nearly all experienced improvements in itch, with 86.8% reporting “very much” or “much” improved itch. Relief was rapid, with 87% noticing improvement in itch within 7 days and 27.5% noticing improvement within 1 day. “This is something I have clinically seen,” Dr. Silverberg said.
After receiving upadacitinib, 87% and 86% of patients indicated they were “extremely” or “very” satisfied with the degree and speed of itch improvement, respectively.
In findings related to skin clearance, 90.7% of respondents reported clearer skin after initiating upadacitinib, with 81.4% reporting “very much” or “much” clearer skin. Skin clearance occurred rapidly, with 30.8% of patients noticing clearer skin within 3 days of starting upadacitinib and 89.2% of patients noticing clearer skin within 14 days. The proportions of patients who were “extremely” or “very” satisfied with the degree and speed of skin clearance were 83.8% and 83.2%, respectively.
“What we’re seeing is that the real-world effectiveness [of upadacitinib] aligns with the clinical trial efficacy,” Dr. Silverberg told this news organization. “This study adds even more data to help inform shared decision-making discussion with our patients in trying to decide what medication is best for them.”
He acknowledged certain limitations of the survey, including the lack of a control group of other treatments for comparison, a low response rate, and the potential for response bias. “That said, I think the results remain important, but we value having even more real-world data in the future from prospective registries,” he said. “Those kinds of studies are ongoing, and we look forward to getting more real-world data readouts.”
AbbVie, the manufacturer of upadacitinib, funded the study. Dr. Silverberg reported having served as an advisor, consultant, speaker, and/or investigator for several pharmaceutical companies, including AbbVie. Two authors are AbbVie employees.
A version of this article appeared on Medscape.com.
, while 7.8% rated their itch as minimally improved.
Also, 27.5% reported itch improvement within one day of taking upadacitinib (Rinvoq), an oral Janus kinase inhibitor that was approved to treat moderate to severe AD in adults and children aged ≥ 12 years in January 2022.
“We have a lot of data about upadacitinib from clinical trials, but sometimes there’s a concern that when you start using a medication in the real world, the effectiveness doesn’t match up with the efficacy observed in clinical trials,” the study’s first author, Jonathan I. Silverberg, MD, PhD, professor of dermatology at George Washington University, Washington, said in an interview after the Revolutionizing Atopic Dermatitis conference, where the study was presented during a late-breaking abstract session. “We always want to confirm or reaffirm clinical trial results with real-world data.”
In SCALE-UP, 6191 adults with moderate to severe AD participating in the patient support program for upadacitinib in the United States were invited to complete a one-time online survey about their experience with upadacitinib, including the degree of and time to itch improvement and skin clearance. The researchers reported on 204 patients who completed the survey questions, for a response rate of 3.3%. The mean age of respondents was 45.3 years, their mean age when diagnosed with AD was 30.3 years; 70.1% were women, and 37% were using topical corticosteroids. In addition, 68.6% were White individuals, 12.3% were Black individuals, 8.8% were Asian individuals or Pacific Islanders, and 0.5% were Native Americans/Alaska Natives.
Duration of upadacitinib treatment was 2-6 months for 50.5% of the patients and 7-12 months for the remaining patients. Starting upadacitinib dose was 15 mg for about 95% of patients and 30 mg for nearly 4% of patients. At the time of the survey, 79.4% of patients were receiving upadacitinib 15 mg once a day, and 19.6% were receiving upadacitinib 30 mg once a day.
Improvements in Itch, Skin Clearance
Nearly all experienced improvements in itch, with 86.8% reporting “very much” or “much” improved itch. Relief was rapid, with 87% noticing improvement in itch within 7 days and 27.5% noticing improvement within 1 day. “This is something I have clinically seen,” Dr. Silverberg said.
After receiving upadacitinib, 87% and 86% of patients indicated they were “extremely” or “very” satisfied with the degree and speed of itch improvement, respectively.
In findings related to skin clearance, 90.7% of respondents reported clearer skin after initiating upadacitinib, with 81.4% reporting “very much” or “much” clearer skin. Skin clearance occurred rapidly, with 30.8% of patients noticing clearer skin within 3 days of starting upadacitinib and 89.2% of patients noticing clearer skin within 14 days. The proportions of patients who were “extremely” or “very” satisfied with the degree and speed of skin clearance were 83.8% and 83.2%, respectively.
“What we’re seeing is that the real-world effectiveness [of upadacitinib] aligns with the clinical trial efficacy,” Dr. Silverberg told this news organization. “This study adds even more data to help inform shared decision-making discussion with our patients in trying to decide what medication is best for them.”
He acknowledged certain limitations of the survey, including the lack of a control group of other treatments for comparison, a low response rate, and the potential for response bias. “That said, I think the results remain important, but we value having even more real-world data in the future from prospective registries,” he said. “Those kinds of studies are ongoing, and we look forward to getting more real-world data readouts.”
AbbVie, the manufacturer of upadacitinib, funded the study. Dr. Silverberg reported having served as an advisor, consultant, speaker, and/or investigator for several pharmaceutical companies, including AbbVie. Two authors are AbbVie employees.
A version of this article appeared on Medscape.com.
, while 7.8% rated their itch as minimally improved.
Also, 27.5% reported itch improvement within one day of taking upadacitinib (Rinvoq), an oral Janus kinase inhibitor that was approved to treat moderate to severe AD in adults and children aged ≥ 12 years in January 2022.
“We have a lot of data about upadacitinib from clinical trials, but sometimes there’s a concern that when you start using a medication in the real world, the effectiveness doesn’t match up with the efficacy observed in clinical trials,” the study’s first author, Jonathan I. Silverberg, MD, PhD, professor of dermatology at George Washington University, Washington, said in an interview after the Revolutionizing Atopic Dermatitis conference, where the study was presented during a late-breaking abstract session. “We always want to confirm or reaffirm clinical trial results with real-world data.”
In SCALE-UP, 6191 adults with moderate to severe AD participating in the patient support program for upadacitinib in the United States were invited to complete a one-time online survey about their experience with upadacitinib, including the degree of and time to itch improvement and skin clearance. The researchers reported on 204 patients who completed the survey questions, for a response rate of 3.3%. The mean age of respondents was 45.3 years, their mean age when diagnosed with AD was 30.3 years; 70.1% were women, and 37% were using topical corticosteroids. In addition, 68.6% were White individuals, 12.3% were Black individuals, 8.8% were Asian individuals or Pacific Islanders, and 0.5% were Native Americans/Alaska Natives.
Duration of upadacitinib treatment was 2-6 months for 50.5% of the patients and 7-12 months for the remaining patients. Starting upadacitinib dose was 15 mg for about 95% of patients and 30 mg for nearly 4% of patients. At the time of the survey, 79.4% of patients were receiving upadacitinib 15 mg once a day, and 19.6% were receiving upadacitinib 30 mg once a day.
Improvements in Itch, Skin Clearance
Nearly all experienced improvements in itch, with 86.8% reporting “very much” or “much” improved itch. Relief was rapid, with 87% noticing improvement in itch within 7 days and 27.5% noticing improvement within 1 day. “This is something I have clinically seen,” Dr. Silverberg said.
After receiving upadacitinib, 87% and 86% of patients indicated they were “extremely” or “very” satisfied with the degree and speed of itch improvement, respectively.
In findings related to skin clearance, 90.7% of respondents reported clearer skin after initiating upadacitinib, with 81.4% reporting “very much” or “much” clearer skin. Skin clearance occurred rapidly, with 30.8% of patients noticing clearer skin within 3 days of starting upadacitinib and 89.2% of patients noticing clearer skin within 14 days. The proportions of patients who were “extremely” or “very” satisfied with the degree and speed of skin clearance were 83.8% and 83.2%, respectively.
“What we’re seeing is that the real-world effectiveness [of upadacitinib] aligns with the clinical trial efficacy,” Dr. Silverberg told this news organization. “This study adds even more data to help inform shared decision-making discussion with our patients in trying to decide what medication is best for them.”
He acknowledged certain limitations of the survey, including the lack of a control group of other treatments for comparison, a low response rate, and the potential for response bias. “That said, I think the results remain important, but we value having even more real-world data in the future from prospective registries,” he said. “Those kinds of studies are ongoing, and we look forward to getting more real-world data readouts.”
AbbVie, the manufacturer of upadacitinib, funded the study. Dr. Silverberg reported having served as an advisor, consultant, speaker, and/or investigator for several pharmaceutical companies, including AbbVie. Two authors are AbbVie employees.
A version of this article appeared on Medscape.com.
Debate Over Axial Involvement in Psoriatic Arthritis Still Unresolved Despite New Studies
VIENNA — While there is no doubt that some people with psoriatic arthritis (PsA) have axial symptoms, data presented at the annual European Congress of Rheumatology do not appear to add much to what is already known about axial PsA or to further the cause of differentiating it from axial spondyloarthritis (axSpA).
In both the AXIS study and Reuma.pt, around one in three patients with PsA were found to have axial involvement. Notably, the percentage of people with axial PsA was found to vary according to how imaging information was interpreted in the AXIS study. Both studies were discussed during the Axial Involvement in PsA and SpA session at EULAR 2024.
The One-Million-Dollar Question
“So, the one-million-dollar question: What is it, really?” Philippe Carron, MD, PhD, Ghent University Hospital, Ghent, Belgium, said in the presentation that started the session. Despite PsA being described more than 60 years ago, “we still have no internationally accepted definition or a consensus on how we should define these patients and how we should screen them,” he said.
“There are some believers that it is just a form of axial SpA with concomitant psoriasis, but also some people that think that the axial PsA is a typical disease, with typical characteristics which are different from axial disease,” Dr. Carron said.
The lack of consensus makes it difficult to estimate just how many people have axial PsA. Reported prevalences range from 5% to 70%, “all caused by which criteria that you’re using to define axial involvement,” Dr. Carron added.
There are, however, two things that can be agreed upon, according to Dr. Carron. First, the prevalence of axial involvement in people with early PsA is “much, much lower” than that of more established disease. Second, exclusive axial involvement is seen in “just a minority of PsA patients.” Most people with axial disease also have peripheral disease, he added.
Imaging findings in axial PsA “are quite similar to those seen in axial SpA,” although Dr. Carron also said that there were some distinct differences. Radiographic sacroiliitis occurs in around 25%-50% of people with axial PsA, and atypical syndesmophytes are more often found in people with axial PsA than in those with axSpA.
Shared Characteristics
But are axial PsA and axSpA separate diseases or part of the same disease continuum? That’s a question that is still very much open for debate, said Sofia Ramiro, MD, PhD, a senior researcher at Leiden University Medical Center, Leiden, the Netherlands, and rheumatology consultant at Zuyderland Medical Center in Heerlen, the Netherlands.
While many studies have looked to answer this question, there is a big methodological problem — the studies largely cannot be compared as they have used different definitions of axSpA.
Take a patient with inflammatory back pain, psoriasis, and oligoarthritis, Dr. Ramiro said. If the patient goes to one rheumatologist, they may get a diagnosis of axSpA, but if they go to a different rheumatologist, they may get a diagnosis of axial PsA.
“This is influenced by training, expertise, by beliefs, and by belonging to ASAS [Assessment of Spondyloarthritis International Society] or to GRAPPA [Group for Research and Assessment of Psoriasis and Psoriatic Arthritis],” Dr. Ramiro suggested. It’s “a diagnostic bias” that is very difficult to overcome and makes direct comparisons between patient populations recruited into clinical studies “extremely challenging.”
To confuse matters more, axial PsA and axSpA share common characteristics: Inflammatory back pain, HLA-B27 positivity, elevated levels of C-reactive protein (CRP) or a higher erythrocyte sedimentation rate, and structural lesions in the sacroiliac joints and spine.
AXIS Study ‘Gives Answers’
More research into factors associated with axial PsA need to be performed to try to help define the condition and enable classification and ultimately treatment guidelines. This is where the AXIS study comes in.
The AXIS study is a joint project of ASAS and GRAPPA that was started in January 2019 with the aim of defining a homogeneous subgroup of patients who could be studied.
“The objectives of the AXIS study are to determine the frequency of axial involvement in patients with PsA; to identify the frequency of active inflammatory and structural changes on imaging; and to identify factors associated with the presence of axial involvement in PsA,” Murat Torgutalp, MD, of Charité – Universitätsmedizin Berlin, Berlin, Germany, said at EULAR 2024.
The study population consisted of 409 consecutively recruited patients diagnosed with PsA according to CASPAR (Classification for Psoriatic Arthritis) criteria; all have had PsA for up to 10 years and were untreated with biologic or targeted synthetic disease modifying drugs at the time of inclusion.
Dr. Torgutalp, who is the study’s primary research coordinator, reported that a diagnosis of PsA was made in 37% of the population when local investigators considered available clinical, laboratory, and imaging data. However, patients’ imaging data were also centrally assessed, and when the local investigators were party to the expert imaging interpretations, the percentage of people diagnosed with PsA dropped to 27%.
“When we looked at the clinical characteristics, the presence of the back pain, particularly inflammatory back pain, HLA-B27 positivity, elevated CRP, and presence of active, inflammatory and structural changes in the sacroiliac joints and spine were associated with the final conclusion on the presence of axial involvement,” Dr. Torgutalp said.
Despite the title of his presentation being “The Axis Study Gives Answers,” Dr. Torgutalp presented lots of data without giving much insight into how they might be used. He concluded that “overall, there was a trend toward overestimation of the presence of imaging changes indicative of axial involvement across all imaging modalities” by the local investigators.
Dennis McGonagle, MB, MCH, BAO, PhD, of the University of Leeds, Leeds, England,said in an interview that the AXIS study “is a noble, international effort across multiple countries to try and better understand axial PsA.”
Dr. McGonagle, who was not involved in the study, added: “A lot of data are being generated, and a lot of analysis needs to be done to drill down to get a clear message that could influence practice.”
Axial PsA in the Portuguese Population
Separately, Catarina Abreu, a rheumatology intern at Hospital Garcia de Orta, Almada, Portugal, presented some real-world data on axial PsA from Reuma.pt.
Of 2304 patients, 854 (37.1%) reportedly had axial PsA, which had been defined as physician-reported spondylitis or the presence of imaging findings suggestive of axial involvement. This included radiographic- or MRI-detected sacroiliitis or syndesmophytes seen on axial x-rays.
The majority (78.2%) of those with an axial PsA diagnosis had concomitant peripheral involvement, with 8.1% having exclusive axial disease.
About 70% of the axial PsA diagnoses had been made using clinical or laboratory findings alone, and 30% of diagnoses was based on imaging results. Of the latter, Ms. Abreu noted that patients who had imaging data available were more likely to be HLA-B27 positive and less likely to have dactylitis, with respective odds ratios (ORs) of 3.10 and 2.42.
Individuals with axial PsA were more likely to have enthesitis (OR, 1.92), although no data were available on whether this was axial or peripheral enthesitis. Tobacco exposure was also linked to an increased chance of having axial PsA (OR, 1.66).
Ms. Abreu noted that the “scarce number of available imaging exams” and other missing data in Reuma.pt may have led to an underdiagnosis of axial PsA.
“The difference that we found between axial and peripheral [PsA] are similar to the differences found in other studies that compared axial psoriatic arthritis with axial spondyloarthritis,” Ms. Abreu said.
“So, we leave with the question that was already left before here: If these are different diseases or just different phenotypes of the same disease, and what implications will this have in the future?” Ms. Abreu concluded.
Dr. Carron received educational grants, speaker fees, or honoraria for other consultancy work from AbbVie, UCB, Pfizer, Eli Lilly, Novartis, Janssen, and Galapagos/Alfasigma. Dr. Ramiro is an ASAS executive committee member and received research grants or consulting/speaker fees from AbbVie, Eli Lilly, Galapagos, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, and UCB. AXIS is supported by unrestricted research grants from AbbVie, Galapagos, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Torgutalp is the primary research coordinator for the study; he reported no financial conflicts of interest. The Reuma.pt registry was developed with the financial support of the pharmaceutical industry and is currently supported by AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, and Sobi. Ms. Abreu reported no financial conflicts of interest.
A version of this article appeared on Medscape.com.
VIENNA — While there is no doubt that some people with psoriatic arthritis (PsA) have axial symptoms, data presented at the annual European Congress of Rheumatology do not appear to add much to what is already known about axial PsA or to further the cause of differentiating it from axial spondyloarthritis (axSpA).
In both the AXIS study and Reuma.pt, around one in three patients with PsA were found to have axial involvement. Notably, the percentage of people with axial PsA was found to vary according to how imaging information was interpreted in the AXIS study. Both studies were discussed during the Axial Involvement in PsA and SpA session at EULAR 2024.
The One-Million-Dollar Question
“So, the one-million-dollar question: What is it, really?” Philippe Carron, MD, PhD, Ghent University Hospital, Ghent, Belgium, said in the presentation that started the session. Despite PsA being described more than 60 years ago, “we still have no internationally accepted definition or a consensus on how we should define these patients and how we should screen them,” he said.
“There are some believers that it is just a form of axial SpA with concomitant psoriasis, but also some people that think that the axial PsA is a typical disease, with typical characteristics which are different from axial disease,” Dr. Carron said.
The lack of consensus makes it difficult to estimate just how many people have axial PsA. Reported prevalences range from 5% to 70%, “all caused by which criteria that you’re using to define axial involvement,” Dr. Carron added.
There are, however, two things that can be agreed upon, according to Dr. Carron. First, the prevalence of axial involvement in people with early PsA is “much, much lower” than that of more established disease. Second, exclusive axial involvement is seen in “just a minority of PsA patients.” Most people with axial disease also have peripheral disease, he added.
Imaging findings in axial PsA “are quite similar to those seen in axial SpA,” although Dr. Carron also said that there were some distinct differences. Radiographic sacroiliitis occurs in around 25%-50% of people with axial PsA, and atypical syndesmophytes are more often found in people with axial PsA than in those with axSpA.
Shared Characteristics
But are axial PsA and axSpA separate diseases or part of the same disease continuum? That’s a question that is still very much open for debate, said Sofia Ramiro, MD, PhD, a senior researcher at Leiden University Medical Center, Leiden, the Netherlands, and rheumatology consultant at Zuyderland Medical Center in Heerlen, the Netherlands.
While many studies have looked to answer this question, there is a big methodological problem — the studies largely cannot be compared as they have used different definitions of axSpA.
Take a patient with inflammatory back pain, psoriasis, and oligoarthritis, Dr. Ramiro said. If the patient goes to one rheumatologist, they may get a diagnosis of axSpA, but if they go to a different rheumatologist, they may get a diagnosis of axial PsA.
“This is influenced by training, expertise, by beliefs, and by belonging to ASAS [Assessment of Spondyloarthritis International Society] or to GRAPPA [Group for Research and Assessment of Psoriasis and Psoriatic Arthritis],” Dr. Ramiro suggested. It’s “a diagnostic bias” that is very difficult to overcome and makes direct comparisons between patient populations recruited into clinical studies “extremely challenging.”
To confuse matters more, axial PsA and axSpA share common characteristics: Inflammatory back pain, HLA-B27 positivity, elevated levels of C-reactive protein (CRP) or a higher erythrocyte sedimentation rate, and structural lesions in the sacroiliac joints and spine.
AXIS Study ‘Gives Answers’
More research into factors associated with axial PsA need to be performed to try to help define the condition and enable classification and ultimately treatment guidelines. This is where the AXIS study comes in.
The AXIS study is a joint project of ASAS and GRAPPA that was started in January 2019 with the aim of defining a homogeneous subgroup of patients who could be studied.
“The objectives of the AXIS study are to determine the frequency of axial involvement in patients with PsA; to identify the frequency of active inflammatory and structural changes on imaging; and to identify factors associated with the presence of axial involvement in PsA,” Murat Torgutalp, MD, of Charité – Universitätsmedizin Berlin, Berlin, Germany, said at EULAR 2024.
The study population consisted of 409 consecutively recruited patients diagnosed with PsA according to CASPAR (Classification for Psoriatic Arthritis) criteria; all have had PsA for up to 10 years and were untreated with biologic or targeted synthetic disease modifying drugs at the time of inclusion.
Dr. Torgutalp, who is the study’s primary research coordinator, reported that a diagnosis of PsA was made in 37% of the population when local investigators considered available clinical, laboratory, and imaging data. However, patients’ imaging data were also centrally assessed, and when the local investigators were party to the expert imaging interpretations, the percentage of people diagnosed with PsA dropped to 27%.
“When we looked at the clinical characteristics, the presence of the back pain, particularly inflammatory back pain, HLA-B27 positivity, elevated CRP, and presence of active, inflammatory and structural changes in the sacroiliac joints and spine were associated with the final conclusion on the presence of axial involvement,” Dr. Torgutalp said.
Despite the title of his presentation being “The Axis Study Gives Answers,” Dr. Torgutalp presented lots of data without giving much insight into how they might be used. He concluded that “overall, there was a trend toward overestimation of the presence of imaging changes indicative of axial involvement across all imaging modalities” by the local investigators.
Dennis McGonagle, MB, MCH, BAO, PhD, of the University of Leeds, Leeds, England,said in an interview that the AXIS study “is a noble, international effort across multiple countries to try and better understand axial PsA.”
Dr. McGonagle, who was not involved in the study, added: “A lot of data are being generated, and a lot of analysis needs to be done to drill down to get a clear message that could influence practice.”
Axial PsA in the Portuguese Population
Separately, Catarina Abreu, a rheumatology intern at Hospital Garcia de Orta, Almada, Portugal, presented some real-world data on axial PsA from Reuma.pt.
Of 2304 patients, 854 (37.1%) reportedly had axial PsA, which had been defined as physician-reported spondylitis or the presence of imaging findings suggestive of axial involvement. This included radiographic- or MRI-detected sacroiliitis or syndesmophytes seen on axial x-rays.
The majority (78.2%) of those with an axial PsA diagnosis had concomitant peripheral involvement, with 8.1% having exclusive axial disease.
About 70% of the axial PsA diagnoses had been made using clinical or laboratory findings alone, and 30% of diagnoses was based on imaging results. Of the latter, Ms. Abreu noted that patients who had imaging data available were more likely to be HLA-B27 positive and less likely to have dactylitis, with respective odds ratios (ORs) of 3.10 and 2.42.
Individuals with axial PsA were more likely to have enthesitis (OR, 1.92), although no data were available on whether this was axial or peripheral enthesitis. Tobacco exposure was also linked to an increased chance of having axial PsA (OR, 1.66).
Ms. Abreu noted that the “scarce number of available imaging exams” and other missing data in Reuma.pt may have led to an underdiagnosis of axial PsA.
“The difference that we found between axial and peripheral [PsA] are similar to the differences found in other studies that compared axial psoriatic arthritis with axial spondyloarthritis,” Ms. Abreu said.
“So, we leave with the question that was already left before here: If these are different diseases or just different phenotypes of the same disease, and what implications will this have in the future?” Ms. Abreu concluded.
Dr. Carron received educational grants, speaker fees, or honoraria for other consultancy work from AbbVie, UCB, Pfizer, Eli Lilly, Novartis, Janssen, and Galapagos/Alfasigma. Dr. Ramiro is an ASAS executive committee member and received research grants or consulting/speaker fees from AbbVie, Eli Lilly, Galapagos, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, and UCB. AXIS is supported by unrestricted research grants from AbbVie, Galapagos, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Torgutalp is the primary research coordinator for the study; he reported no financial conflicts of interest. The Reuma.pt registry was developed with the financial support of the pharmaceutical industry and is currently supported by AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, and Sobi. Ms. Abreu reported no financial conflicts of interest.
A version of this article appeared on Medscape.com.
VIENNA — While there is no doubt that some people with psoriatic arthritis (PsA) have axial symptoms, data presented at the annual European Congress of Rheumatology do not appear to add much to what is already known about axial PsA or to further the cause of differentiating it from axial spondyloarthritis (axSpA).
In both the AXIS study and Reuma.pt, around one in three patients with PsA were found to have axial involvement. Notably, the percentage of people with axial PsA was found to vary according to how imaging information was interpreted in the AXIS study. Both studies were discussed during the Axial Involvement in PsA and SpA session at EULAR 2024.
The One-Million-Dollar Question
“So, the one-million-dollar question: What is it, really?” Philippe Carron, MD, PhD, Ghent University Hospital, Ghent, Belgium, said in the presentation that started the session. Despite PsA being described more than 60 years ago, “we still have no internationally accepted definition or a consensus on how we should define these patients and how we should screen them,” he said.
“There are some believers that it is just a form of axial SpA with concomitant psoriasis, but also some people that think that the axial PsA is a typical disease, with typical characteristics which are different from axial disease,” Dr. Carron said.
The lack of consensus makes it difficult to estimate just how many people have axial PsA. Reported prevalences range from 5% to 70%, “all caused by which criteria that you’re using to define axial involvement,” Dr. Carron added.
There are, however, two things that can be agreed upon, according to Dr. Carron. First, the prevalence of axial involvement in people with early PsA is “much, much lower” than that of more established disease. Second, exclusive axial involvement is seen in “just a minority of PsA patients.” Most people with axial disease also have peripheral disease, he added.
Imaging findings in axial PsA “are quite similar to those seen in axial SpA,” although Dr. Carron also said that there were some distinct differences. Radiographic sacroiliitis occurs in around 25%-50% of people with axial PsA, and atypical syndesmophytes are more often found in people with axial PsA than in those with axSpA.
Shared Characteristics
But are axial PsA and axSpA separate diseases or part of the same disease continuum? That’s a question that is still very much open for debate, said Sofia Ramiro, MD, PhD, a senior researcher at Leiden University Medical Center, Leiden, the Netherlands, and rheumatology consultant at Zuyderland Medical Center in Heerlen, the Netherlands.
While many studies have looked to answer this question, there is a big methodological problem — the studies largely cannot be compared as they have used different definitions of axSpA.
Take a patient with inflammatory back pain, psoriasis, and oligoarthritis, Dr. Ramiro said. If the patient goes to one rheumatologist, they may get a diagnosis of axSpA, but if they go to a different rheumatologist, they may get a diagnosis of axial PsA.
“This is influenced by training, expertise, by beliefs, and by belonging to ASAS [Assessment of Spondyloarthritis International Society] or to GRAPPA [Group for Research and Assessment of Psoriasis and Psoriatic Arthritis],” Dr. Ramiro suggested. It’s “a diagnostic bias” that is very difficult to overcome and makes direct comparisons between patient populations recruited into clinical studies “extremely challenging.”
To confuse matters more, axial PsA and axSpA share common characteristics: Inflammatory back pain, HLA-B27 positivity, elevated levels of C-reactive protein (CRP) or a higher erythrocyte sedimentation rate, and structural lesions in the sacroiliac joints and spine.
AXIS Study ‘Gives Answers’
More research into factors associated with axial PsA need to be performed to try to help define the condition and enable classification and ultimately treatment guidelines. This is where the AXIS study comes in.
The AXIS study is a joint project of ASAS and GRAPPA that was started in January 2019 with the aim of defining a homogeneous subgroup of patients who could be studied.
“The objectives of the AXIS study are to determine the frequency of axial involvement in patients with PsA; to identify the frequency of active inflammatory and structural changes on imaging; and to identify factors associated with the presence of axial involvement in PsA,” Murat Torgutalp, MD, of Charité – Universitätsmedizin Berlin, Berlin, Germany, said at EULAR 2024.
The study population consisted of 409 consecutively recruited patients diagnosed with PsA according to CASPAR (Classification for Psoriatic Arthritis) criteria; all have had PsA for up to 10 years and were untreated with biologic or targeted synthetic disease modifying drugs at the time of inclusion.
Dr. Torgutalp, who is the study’s primary research coordinator, reported that a diagnosis of PsA was made in 37% of the population when local investigators considered available clinical, laboratory, and imaging data. However, patients’ imaging data were also centrally assessed, and when the local investigators were party to the expert imaging interpretations, the percentage of people diagnosed with PsA dropped to 27%.
“When we looked at the clinical characteristics, the presence of the back pain, particularly inflammatory back pain, HLA-B27 positivity, elevated CRP, and presence of active, inflammatory and structural changes in the sacroiliac joints and spine were associated with the final conclusion on the presence of axial involvement,” Dr. Torgutalp said.
Despite the title of his presentation being “The Axis Study Gives Answers,” Dr. Torgutalp presented lots of data without giving much insight into how they might be used. He concluded that “overall, there was a trend toward overestimation of the presence of imaging changes indicative of axial involvement across all imaging modalities” by the local investigators.
Dennis McGonagle, MB, MCH, BAO, PhD, of the University of Leeds, Leeds, England,said in an interview that the AXIS study “is a noble, international effort across multiple countries to try and better understand axial PsA.”
Dr. McGonagle, who was not involved in the study, added: “A lot of data are being generated, and a lot of analysis needs to be done to drill down to get a clear message that could influence practice.”
Axial PsA in the Portuguese Population
Separately, Catarina Abreu, a rheumatology intern at Hospital Garcia de Orta, Almada, Portugal, presented some real-world data on axial PsA from Reuma.pt.
Of 2304 patients, 854 (37.1%) reportedly had axial PsA, which had been defined as physician-reported spondylitis or the presence of imaging findings suggestive of axial involvement. This included radiographic- or MRI-detected sacroiliitis or syndesmophytes seen on axial x-rays.
The majority (78.2%) of those with an axial PsA diagnosis had concomitant peripheral involvement, with 8.1% having exclusive axial disease.
About 70% of the axial PsA diagnoses had been made using clinical or laboratory findings alone, and 30% of diagnoses was based on imaging results. Of the latter, Ms. Abreu noted that patients who had imaging data available were more likely to be HLA-B27 positive and less likely to have dactylitis, with respective odds ratios (ORs) of 3.10 and 2.42.
Individuals with axial PsA were more likely to have enthesitis (OR, 1.92), although no data were available on whether this was axial or peripheral enthesitis. Tobacco exposure was also linked to an increased chance of having axial PsA (OR, 1.66).
Ms. Abreu noted that the “scarce number of available imaging exams” and other missing data in Reuma.pt may have led to an underdiagnosis of axial PsA.
“The difference that we found between axial and peripheral [PsA] are similar to the differences found in other studies that compared axial psoriatic arthritis with axial spondyloarthritis,” Ms. Abreu said.
“So, we leave with the question that was already left before here: If these are different diseases or just different phenotypes of the same disease, and what implications will this have in the future?” Ms. Abreu concluded.
Dr. Carron received educational grants, speaker fees, or honoraria for other consultancy work from AbbVie, UCB, Pfizer, Eli Lilly, Novartis, Janssen, and Galapagos/Alfasigma. Dr. Ramiro is an ASAS executive committee member and received research grants or consulting/speaker fees from AbbVie, Eli Lilly, Galapagos, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, and UCB. AXIS is supported by unrestricted research grants from AbbVie, Galapagos, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Torgutalp is the primary research coordinator for the study; he reported no financial conflicts of interest. The Reuma.pt registry was developed with the financial support of the pharmaceutical industry and is currently supported by AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, and Sobi. Ms. Abreu reported no financial conflicts of interest.
A version of this article appeared on Medscape.com.
FROM EULAR 2024
EMA Greenlights Four Drugs for Bladder and Other Cancers
Balversa
The CHMP endorsed the approval of Balversa (erdafitinib, Janssen-Cilag International N.V.), intended for the treatment of urothelial carcinoma, a type of cancer affecting the bladder and urinary system.
As a monotherapy, Balversa is indicated for the treatment of adult patients with unresectable or metastatic urothelial carcinoma harboring susceptible FGFR3 genetic alterations. These patients must have previously received at least one line of therapy containing a programmed death receptor 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor in the unresectable or metastatic treatment setting.
Urothelial carcinoma is the most common form of bladder cancer, the ninth most frequently diagnosed cancer worldwide. In 2022, there were approximately 614,000 new cases of bladder cancer and 220,000 deaths globally.
The highest incidence rates in both men and women are found in Southern Europe. Greece had 5800 new cases and 1537 deaths in 2018. Spain has the highest incidence rate in men globally. Since the 1990s, bladder cancer incidence trends have diverged by sex, with rates decreasing or stabilizing in men but increasing among women in certain European countries.
The CHMP recommendation is based on data from cohort 1 of the phase 3 THOR trial, which compared erdafitinib with standard-of-care chemotherapy (investigator’s choice of docetaxel or vinflunine). Cohort 1 included 266 adults with advanced urothelial cancer harboring selected FGFR3 alterations.
All patients had disease progression after one or two prior treatments, at least one of which included a PD-1 or PD-L1 inhibitor. The major efficacy endpoints were overall survival, progression free survival, and objective response rate (ORR).
Treatment with erdafitinib reduced the risk for death by 36% compared with chemotherapy (hazard ratio [HR], 0.64; P = .005). Median overall survival was 12.1 months in the erdafitinib arm vs 7.8 months in the chemotherapy arm. Median progression-free survival was 5.6 months in the erdafitinib arm vs 2.7 months in the chemotherapy arm (HR, 0.58; P = .0002). ORR was 35.3% with erdafitinib compared with 8.5% with chemotherapy.
Balversa will be available as 3-mg, 4-mg, and 5-mg film-coated tablets. Erdafitinib, the active substance in Balversa, is an antineoplastic protein kinase inhibitor that suppresses fibroblast growth factor receptor (FGFR) tyrosine kinases. Deregulation of FGFR3 signaling is implicated in the pathogenesis of urothelial cancer, and FGFR inhibition has demonstrated antitumor activity in FGFR-expressing cells.
Ordspono
The committee adopted a positive opinion for Ordspono (odronextamab, Regeneron Ireland Designated Activity Company), indicated as a monotherapy for the treatment of adult patients with:
- Relapsed or refractory follicular lymphoma (rrFL), after two or more lines of systemic therapy.
- Relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL), after two or more lines of systemic therapy.
The approval recommendation is based on phase 2 trials (NCT02290951, NCT03888105), which demonstrated high ORRs in patients with rrFL and rrDLBCL.
In the DLBCL cohort, a 49% ORR was achieved in heavily pretreated patients who had not received chimeric antigen receptor T-cell therapy. A total of 31% achieved a complete response.
The FL cohort showed an 82% response rate in patients with grades I-IIIA disease, with 75% of the overall population achieving a complete response.
Ordspono will be available as a 2-mg, 80-mg, and 320-mg concentrate for solution for infusion. The active substance of Ordspono is odronextamab, a bispecific antibody that targets CD20-expressing B cells and CD3-expressing T cells. By binding to both, it induces T-cell activation and generates a polyclonal cytotoxic T-cell response, leading to the lysis of malignant B cells.
Generics
The panel also adopted positive opinions for two generic cancer medicines.
Enzalutamide Viatris (enzalutamide) is indicated for the treatment of adult men with prostate cancer in several scenarios:
- As monotherapy or with androgen-deprivation therapy for high-risk biochemical recurrent nonmetastatic hormone-sensitive prostate cancer in men unsuitable for salvage-radiotherapy.
- In combination with androgen-deprivation therapy for metastatic hormone-sensitive prostate cancer.
- For high-risk nonmetastatic castration-resistant prostate cancer (CRPC).
- For metastatic CRPC in men who are asymptomatic or mildly symptomatic after failure of androgen-deprivation therapy, where chemotherapy is not yet indicated.
- For metastatic CRPC in men whose disease has progressed on or after docetaxel therapy.
Enzalutamide Viatris is a generic version of Xtandi, authorized in the European Union since June 2013. Studies have confirmed the satisfactory quality and bioequivalence of Enzalutamide Viatris to Xtandi.
Enzalutamide Viatris will be available as 40-mg and 80-mg film-coated tablets. The active substance of Enzalutamide Viatris is enzalutamide, a hormone antagonist that blocks multiple steps in the androgen receptor–signaling pathway.
Nilotinib Accord (nilotinib) is indicated for the treatment of Philadelphia chromosome–positive chronic myelogenous leukemia (CML).
It is used in adult and pediatric patients with newly diagnosed CML in the chronic phase, adult patients with chronic phase and accelerated phase CML with resistance or intolerance to prior therapy including imatinib, and pediatric patients with CML with resistance or intolerance to prior therapy including imatinib.
Nilotinib Accord is a generic of Tasigna, authorized in the European Union since November 2007. Studies have demonstrated the satisfactory quality and bioequivalence of Nilotinib Accord to Tasigna.
Nilotinib Accord will be available as 50-mg, 150-mg, and 200-mg hard capsules. The active substance of Nilotinib Accord is nilotinib, an antineoplastic protein kinase inhibitor that targets BCR-ABL kinase and other oncogenic kinases.
A version of this article appeared on Medscape.com.
Balversa
The CHMP endorsed the approval of Balversa (erdafitinib, Janssen-Cilag International N.V.), intended for the treatment of urothelial carcinoma, a type of cancer affecting the bladder and urinary system.
As a monotherapy, Balversa is indicated for the treatment of adult patients with unresectable or metastatic urothelial carcinoma harboring susceptible FGFR3 genetic alterations. These patients must have previously received at least one line of therapy containing a programmed death receptor 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor in the unresectable or metastatic treatment setting.
Urothelial carcinoma is the most common form of bladder cancer, the ninth most frequently diagnosed cancer worldwide. In 2022, there were approximately 614,000 new cases of bladder cancer and 220,000 deaths globally.
The highest incidence rates in both men and women are found in Southern Europe. Greece had 5800 new cases and 1537 deaths in 2018. Spain has the highest incidence rate in men globally. Since the 1990s, bladder cancer incidence trends have diverged by sex, with rates decreasing or stabilizing in men but increasing among women in certain European countries.
The CHMP recommendation is based on data from cohort 1 of the phase 3 THOR trial, which compared erdafitinib with standard-of-care chemotherapy (investigator’s choice of docetaxel or vinflunine). Cohort 1 included 266 adults with advanced urothelial cancer harboring selected FGFR3 alterations.
All patients had disease progression after one or two prior treatments, at least one of which included a PD-1 or PD-L1 inhibitor. The major efficacy endpoints were overall survival, progression free survival, and objective response rate (ORR).
Treatment with erdafitinib reduced the risk for death by 36% compared with chemotherapy (hazard ratio [HR], 0.64; P = .005). Median overall survival was 12.1 months in the erdafitinib arm vs 7.8 months in the chemotherapy arm. Median progression-free survival was 5.6 months in the erdafitinib arm vs 2.7 months in the chemotherapy arm (HR, 0.58; P = .0002). ORR was 35.3% with erdafitinib compared with 8.5% with chemotherapy.
Balversa will be available as 3-mg, 4-mg, and 5-mg film-coated tablets. Erdafitinib, the active substance in Balversa, is an antineoplastic protein kinase inhibitor that suppresses fibroblast growth factor receptor (FGFR) tyrosine kinases. Deregulation of FGFR3 signaling is implicated in the pathogenesis of urothelial cancer, and FGFR inhibition has demonstrated antitumor activity in FGFR-expressing cells.
Ordspono
The committee adopted a positive opinion for Ordspono (odronextamab, Regeneron Ireland Designated Activity Company), indicated as a monotherapy for the treatment of adult patients with:
- Relapsed or refractory follicular lymphoma (rrFL), after two or more lines of systemic therapy.
- Relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL), after two or more lines of systemic therapy.
The approval recommendation is based on phase 2 trials (NCT02290951, NCT03888105), which demonstrated high ORRs in patients with rrFL and rrDLBCL.
In the DLBCL cohort, a 49% ORR was achieved in heavily pretreated patients who had not received chimeric antigen receptor T-cell therapy. A total of 31% achieved a complete response.
The FL cohort showed an 82% response rate in patients with grades I-IIIA disease, with 75% of the overall population achieving a complete response.
Ordspono will be available as a 2-mg, 80-mg, and 320-mg concentrate for solution for infusion. The active substance of Ordspono is odronextamab, a bispecific antibody that targets CD20-expressing B cells and CD3-expressing T cells. By binding to both, it induces T-cell activation and generates a polyclonal cytotoxic T-cell response, leading to the lysis of malignant B cells.
Generics
The panel also adopted positive opinions for two generic cancer medicines.
Enzalutamide Viatris (enzalutamide) is indicated for the treatment of adult men with prostate cancer in several scenarios:
- As monotherapy or with androgen-deprivation therapy for high-risk biochemical recurrent nonmetastatic hormone-sensitive prostate cancer in men unsuitable for salvage-radiotherapy.
- In combination with androgen-deprivation therapy for metastatic hormone-sensitive prostate cancer.
- For high-risk nonmetastatic castration-resistant prostate cancer (CRPC).
- For metastatic CRPC in men who are asymptomatic or mildly symptomatic after failure of androgen-deprivation therapy, where chemotherapy is not yet indicated.
- For metastatic CRPC in men whose disease has progressed on or after docetaxel therapy.
Enzalutamide Viatris is a generic version of Xtandi, authorized in the European Union since June 2013. Studies have confirmed the satisfactory quality and bioequivalence of Enzalutamide Viatris to Xtandi.
Enzalutamide Viatris will be available as 40-mg and 80-mg film-coated tablets. The active substance of Enzalutamide Viatris is enzalutamide, a hormone antagonist that blocks multiple steps in the androgen receptor–signaling pathway.
Nilotinib Accord (nilotinib) is indicated for the treatment of Philadelphia chromosome–positive chronic myelogenous leukemia (CML).
It is used in adult and pediatric patients with newly diagnosed CML in the chronic phase, adult patients with chronic phase and accelerated phase CML with resistance or intolerance to prior therapy including imatinib, and pediatric patients with CML with resistance or intolerance to prior therapy including imatinib.
Nilotinib Accord is a generic of Tasigna, authorized in the European Union since November 2007. Studies have demonstrated the satisfactory quality and bioequivalence of Nilotinib Accord to Tasigna.
Nilotinib Accord will be available as 50-mg, 150-mg, and 200-mg hard capsules. The active substance of Nilotinib Accord is nilotinib, an antineoplastic protein kinase inhibitor that targets BCR-ABL kinase and other oncogenic kinases.
A version of this article appeared on Medscape.com.
Balversa
The CHMP endorsed the approval of Balversa (erdafitinib, Janssen-Cilag International N.V.), intended for the treatment of urothelial carcinoma, a type of cancer affecting the bladder and urinary system.
As a monotherapy, Balversa is indicated for the treatment of adult patients with unresectable or metastatic urothelial carcinoma harboring susceptible FGFR3 genetic alterations. These patients must have previously received at least one line of therapy containing a programmed death receptor 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor in the unresectable or metastatic treatment setting.
Urothelial carcinoma is the most common form of bladder cancer, the ninth most frequently diagnosed cancer worldwide. In 2022, there were approximately 614,000 new cases of bladder cancer and 220,000 deaths globally.
The highest incidence rates in both men and women are found in Southern Europe. Greece had 5800 new cases and 1537 deaths in 2018. Spain has the highest incidence rate in men globally. Since the 1990s, bladder cancer incidence trends have diverged by sex, with rates decreasing or stabilizing in men but increasing among women in certain European countries.
The CHMP recommendation is based on data from cohort 1 of the phase 3 THOR trial, which compared erdafitinib with standard-of-care chemotherapy (investigator’s choice of docetaxel or vinflunine). Cohort 1 included 266 adults with advanced urothelial cancer harboring selected FGFR3 alterations.
All patients had disease progression after one or two prior treatments, at least one of which included a PD-1 or PD-L1 inhibitor. The major efficacy endpoints were overall survival, progression free survival, and objective response rate (ORR).
Treatment with erdafitinib reduced the risk for death by 36% compared with chemotherapy (hazard ratio [HR], 0.64; P = .005). Median overall survival was 12.1 months in the erdafitinib arm vs 7.8 months in the chemotherapy arm. Median progression-free survival was 5.6 months in the erdafitinib arm vs 2.7 months in the chemotherapy arm (HR, 0.58; P = .0002). ORR was 35.3% with erdafitinib compared with 8.5% with chemotherapy.
Balversa will be available as 3-mg, 4-mg, and 5-mg film-coated tablets. Erdafitinib, the active substance in Balversa, is an antineoplastic protein kinase inhibitor that suppresses fibroblast growth factor receptor (FGFR) tyrosine kinases. Deregulation of FGFR3 signaling is implicated in the pathogenesis of urothelial cancer, and FGFR inhibition has demonstrated antitumor activity in FGFR-expressing cells.
Ordspono
The committee adopted a positive opinion for Ordspono (odronextamab, Regeneron Ireland Designated Activity Company), indicated as a monotherapy for the treatment of adult patients with:
- Relapsed or refractory follicular lymphoma (rrFL), after two or more lines of systemic therapy.
- Relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL), after two or more lines of systemic therapy.
The approval recommendation is based on phase 2 trials (NCT02290951, NCT03888105), which demonstrated high ORRs in patients with rrFL and rrDLBCL.
In the DLBCL cohort, a 49% ORR was achieved in heavily pretreated patients who had not received chimeric antigen receptor T-cell therapy. A total of 31% achieved a complete response.
The FL cohort showed an 82% response rate in patients with grades I-IIIA disease, with 75% of the overall population achieving a complete response.
Ordspono will be available as a 2-mg, 80-mg, and 320-mg concentrate for solution for infusion. The active substance of Ordspono is odronextamab, a bispecific antibody that targets CD20-expressing B cells and CD3-expressing T cells. By binding to both, it induces T-cell activation and generates a polyclonal cytotoxic T-cell response, leading to the lysis of malignant B cells.
Generics
The panel also adopted positive opinions for two generic cancer medicines.
Enzalutamide Viatris (enzalutamide) is indicated for the treatment of adult men with prostate cancer in several scenarios:
- As monotherapy or with androgen-deprivation therapy for high-risk biochemical recurrent nonmetastatic hormone-sensitive prostate cancer in men unsuitable for salvage-radiotherapy.
- In combination with androgen-deprivation therapy for metastatic hormone-sensitive prostate cancer.
- For high-risk nonmetastatic castration-resistant prostate cancer (CRPC).
- For metastatic CRPC in men who are asymptomatic or mildly symptomatic after failure of androgen-deprivation therapy, where chemotherapy is not yet indicated.
- For metastatic CRPC in men whose disease has progressed on or after docetaxel therapy.
Enzalutamide Viatris is a generic version of Xtandi, authorized in the European Union since June 2013. Studies have confirmed the satisfactory quality and bioequivalence of Enzalutamide Viatris to Xtandi.
Enzalutamide Viatris will be available as 40-mg and 80-mg film-coated tablets. The active substance of Enzalutamide Viatris is enzalutamide, a hormone antagonist that blocks multiple steps in the androgen receptor–signaling pathway.
Nilotinib Accord (nilotinib) is indicated for the treatment of Philadelphia chromosome–positive chronic myelogenous leukemia (CML).
It is used in adult and pediatric patients with newly diagnosed CML in the chronic phase, adult patients with chronic phase and accelerated phase CML with resistance or intolerance to prior therapy including imatinib, and pediatric patients with CML with resistance or intolerance to prior therapy including imatinib.
Nilotinib Accord is a generic of Tasigna, authorized in the European Union since November 2007. Studies have demonstrated the satisfactory quality and bioequivalence of Nilotinib Accord to Tasigna.
Nilotinib Accord will be available as 50-mg, 150-mg, and 200-mg hard capsules. The active substance of Nilotinib Accord is nilotinib, an antineoplastic protein kinase inhibitor that targets BCR-ABL kinase and other oncogenic kinases.
A version of this article appeared on Medscape.com.
AML: Shorter Venetoclax Course Shows Promise for Some
However, the azacitidine plus venetoclax therapy — the “7+7” regimen — was associated with lower platelet transfusion requirements and lower 8-week mortality, suggesting the regimen might be preferable in certain patient populations, Alexandre Bazinet, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.
The composite complete remission (CRc) rate, including complete remission with or without complete count recovery, was identical at 72% among 82 patients treated with the 7+7 regimen and 166 treated with standard therapy, and the complete remission (CR) rate was 57% and 55%, respectively, Dr. Bazinet said.
The median number of cycles to first response was one in both groups, but 42% of responders in the 7+7 group required more than one cycle to achieve their first response, compared with just 1% of those in the standard therapy group, he noted, adding that the median number of cycles to achieve best response was two in the 7+7 group and one in the standard therapy group.
The mortality rate at 4 weeks was similar in the groups (2% vs 5% for 7+7 vs standard therapy), but at 8 weeks, the mortality rate was significantly higher in the standard therapy group (6% vs 16%, respectively). Median overall survival (OS) was 11.2 months versus 10.3 months, and median 2-year survival was 27.7% versus 33.6% in the groups, respectively.
Event-free survival was 6.5 versus 7.4 months, and 2-year event-free survival was 24.5% versus 27.0%, respectively.
Of note, fewer patients in the 7+7 group required platelet transfusions during cycle 1 (62% vs 77%) and the cycle 1 rates of neutropenic fever and red cell transfusion requirements were similar in the two treatment groups, Dr. Bazinet said.
Study participants were 82 adults from seven centers in France who received the 7+7 regimen, and 166 adults from MD Anderson who received standard therapy with a hypomethylating agent plus venetoclax doublets given for 21-28 days during induction. Preliminary data on the 7+7 regimen in patients from the French centers were reported previously and “suggested preserved efficacy with potentially less toxicity,” he noted.
“A hypomethylating agent plus venetoclax doublets are standard-of-care in patients with AML who are older or ineligible for chemotherapy due to comorbidities,” Dr. Bazinet explained, adding that although the venetoclax label calls for 28 days of drug per cycle, shorter courses of 14 to 21 days are commonly used.
These findings are limited by the retrospective study design and by small patient numbers in many subgroups, he said.
“In addition, the cohorts were heterogeneous, consisting of patients treated with a variety of different regimens and across multiple centers and countries. The distribution of FLT3-ITD and NRAS/KRAS mutations differed significantly between cohorts,” he explained, also noting that prophylactic azole use differed across the cohort. “Furthermore, analysis of the toxicity results was also limited by likely differing transfusion polices in different centers.”
Overall, however, the findings suggest that reducing the duration of venetoclax is safe and results in similar CRc rates, although responses may be faster with standard dosing, he said, adding that “7+7 is potentially less toxic and is attractive in patients who are more frail or at risk for complications.”
“Our data support further study of shorter venetoclax duration, within emerging triplet regimens in patients with intermediate or low predictive benefit to mitigate toxicity,” he concluded.
Dr. Bazinet reported having no disclosures.
However, the azacitidine plus venetoclax therapy — the “7+7” regimen — was associated with lower platelet transfusion requirements and lower 8-week mortality, suggesting the regimen might be preferable in certain patient populations, Alexandre Bazinet, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.
The composite complete remission (CRc) rate, including complete remission with or without complete count recovery, was identical at 72% among 82 patients treated with the 7+7 regimen and 166 treated with standard therapy, and the complete remission (CR) rate was 57% and 55%, respectively, Dr. Bazinet said.
The median number of cycles to first response was one in both groups, but 42% of responders in the 7+7 group required more than one cycle to achieve their first response, compared with just 1% of those in the standard therapy group, he noted, adding that the median number of cycles to achieve best response was two in the 7+7 group and one in the standard therapy group.
The mortality rate at 4 weeks was similar in the groups (2% vs 5% for 7+7 vs standard therapy), but at 8 weeks, the mortality rate was significantly higher in the standard therapy group (6% vs 16%, respectively). Median overall survival (OS) was 11.2 months versus 10.3 months, and median 2-year survival was 27.7% versus 33.6% in the groups, respectively.
Event-free survival was 6.5 versus 7.4 months, and 2-year event-free survival was 24.5% versus 27.0%, respectively.
Of note, fewer patients in the 7+7 group required platelet transfusions during cycle 1 (62% vs 77%) and the cycle 1 rates of neutropenic fever and red cell transfusion requirements were similar in the two treatment groups, Dr. Bazinet said.
Study participants were 82 adults from seven centers in France who received the 7+7 regimen, and 166 adults from MD Anderson who received standard therapy with a hypomethylating agent plus venetoclax doublets given for 21-28 days during induction. Preliminary data on the 7+7 regimen in patients from the French centers were reported previously and “suggested preserved efficacy with potentially less toxicity,” he noted.
“A hypomethylating agent plus venetoclax doublets are standard-of-care in patients with AML who are older or ineligible for chemotherapy due to comorbidities,” Dr. Bazinet explained, adding that although the venetoclax label calls for 28 days of drug per cycle, shorter courses of 14 to 21 days are commonly used.
These findings are limited by the retrospective study design and by small patient numbers in many subgroups, he said.
“In addition, the cohorts were heterogeneous, consisting of patients treated with a variety of different regimens and across multiple centers and countries. The distribution of FLT3-ITD and NRAS/KRAS mutations differed significantly between cohorts,” he explained, also noting that prophylactic azole use differed across the cohort. “Furthermore, analysis of the toxicity results was also limited by likely differing transfusion polices in different centers.”
Overall, however, the findings suggest that reducing the duration of venetoclax is safe and results in similar CRc rates, although responses may be faster with standard dosing, he said, adding that “7+7 is potentially less toxic and is attractive in patients who are more frail or at risk for complications.”
“Our data support further study of shorter venetoclax duration, within emerging triplet regimens in patients with intermediate or low predictive benefit to mitigate toxicity,” he concluded.
Dr. Bazinet reported having no disclosures.
However, the azacitidine plus venetoclax therapy — the “7+7” regimen — was associated with lower platelet transfusion requirements and lower 8-week mortality, suggesting the regimen might be preferable in certain patient populations, Alexandre Bazinet, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.
The composite complete remission (CRc) rate, including complete remission with or without complete count recovery, was identical at 72% among 82 patients treated with the 7+7 regimen and 166 treated with standard therapy, and the complete remission (CR) rate was 57% and 55%, respectively, Dr. Bazinet said.
The median number of cycles to first response was one in both groups, but 42% of responders in the 7+7 group required more than one cycle to achieve their first response, compared with just 1% of those in the standard therapy group, he noted, adding that the median number of cycles to achieve best response was two in the 7+7 group and one in the standard therapy group.
The mortality rate at 4 weeks was similar in the groups (2% vs 5% for 7+7 vs standard therapy), but at 8 weeks, the mortality rate was significantly higher in the standard therapy group (6% vs 16%, respectively). Median overall survival (OS) was 11.2 months versus 10.3 months, and median 2-year survival was 27.7% versus 33.6% in the groups, respectively.
Event-free survival was 6.5 versus 7.4 months, and 2-year event-free survival was 24.5% versus 27.0%, respectively.
Of note, fewer patients in the 7+7 group required platelet transfusions during cycle 1 (62% vs 77%) and the cycle 1 rates of neutropenic fever and red cell transfusion requirements were similar in the two treatment groups, Dr. Bazinet said.
Study participants were 82 adults from seven centers in France who received the 7+7 regimen, and 166 adults from MD Anderson who received standard therapy with a hypomethylating agent plus venetoclax doublets given for 21-28 days during induction. Preliminary data on the 7+7 regimen in patients from the French centers were reported previously and “suggested preserved efficacy with potentially less toxicity,” he noted.
“A hypomethylating agent plus venetoclax doublets are standard-of-care in patients with AML who are older or ineligible for chemotherapy due to comorbidities,” Dr. Bazinet explained, adding that although the venetoclax label calls for 28 days of drug per cycle, shorter courses of 14 to 21 days are commonly used.
These findings are limited by the retrospective study design and by small patient numbers in many subgroups, he said.
“In addition, the cohorts were heterogeneous, consisting of patients treated with a variety of different regimens and across multiple centers and countries. The distribution of FLT3-ITD and NRAS/KRAS mutations differed significantly between cohorts,” he explained, also noting that prophylactic azole use differed across the cohort. “Furthermore, analysis of the toxicity results was also limited by likely differing transfusion polices in different centers.”
Overall, however, the findings suggest that reducing the duration of venetoclax is safe and results in similar CRc rates, although responses may be faster with standard dosing, he said, adding that “7+7 is potentially less toxic and is attractive in patients who are more frail or at risk for complications.”
“Our data support further study of shorter venetoclax duration, within emerging triplet regimens in patients with intermediate or low predictive benefit to mitigate toxicity,” he concluded.
Dr. Bazinet reported having no disclosures.
FROM ASCO 2024
Eptinezumab Inhibitor Fails Cluster Headache Test
SAN DIEGO — However, the drug met secondary outcomes of reduction in weekly attacks, mean change in baseline pain, and Patient Global Impression of Change (PGIC) score.
Eptinezumab is the latest of multiple anti–calcitonin gene-related peptide (CGRP) therapies to fail in the clinic against episodic cluster headache, all using weekly attacks as a primary endpoint, though therapies also scored positive results for secondary endpoints, according to Stewart Tepper, MD, who presented the study results at the annual meeting of the American Headache Society
Eptinezumab is already approved for migraine, and is fully bioavailable by the end of an infusion. “That was why we thought this might be a really interesting treatment for prevention of cluster headache,” said Dr. Tepper, who is VP of external research at the New England Institute for Neurology and Headache in Stamford, Connecticut.
Are We Looking at the Wrong Endpoint?
Secondary endpoints offered more encouragement. “For each week, the eptinezumab looked either numerically higher than the placebo or nominal statistical significance was achieved. By week 4, two-thirds of the patients had at least a 50% reduction in their number of weekly cluster attacks. Then the average pain intensity for the day and the patient global impression of change were all in favor of eptinezumab. That made us interested in whether we’re missing something, whether this is maybe not the correct endpoint to be looking at,” said Dr. Tepper.
He suggested that it may be time for the Food and Drug Administration (FDA) to reconsider the endpoints used in clinical trials for cluster headaches.
Study criteria included cluster periods that lasted at least 6 weeks, and at least 1 year since the diagnosis of episodic cluster headache. The study enrolled patients who were out of their cluster period, who underwent a second screening of 7-14 days after they entered a new cycle. After that, they were randomized to an injection of placebo or 400 mg eptinezumab, and followed for 4 weeks. After 4 weeks, all patients received an injection of 400 mg eptinezumab and placebo patients were crossed over to eptinezumab and followed out to 24 weeks.
The study population included 231 patients (78% male; mean age, 44 years), with a mean of 2.7 cluster headache attacks per day an average duration of 62 minutes per attack. The worst pain was reported as excruciating in 59% of participants.
The mean change in number of weekly attacks in weeks 1 and 2, compared with baseline, was not statistically significant (–4.6 with eptinezumab, –4.6 with placebo; P = .5048). More patients in the eptinezumab group had a 50% or greater reduction in attack frequency in weeks 3 (50.9% vs 37.3%; P < .05), week 3 (62.5% vs 43.8%; P < .01), and week 4 (66.7% vs 50.5%; P < .01). The difference in mean change in pain from baseline became statistically significant at week 3 and 4 (P < .01). There were also statistically significant differences in PGIC score at weeks 1, 2, and 4. The frequency of any treatment-emergent adverse event was similar in the eptinezumab and placebo groups (25.0% vs 26.5%), and only one led to treatment withdrawal in the eptinezumab group (0.9%).
Thoughts on Redesigning Cluster Headache Clinical Trials
During the Q&A session, Andrea Harriott, MD, PhD, a neurologist at Massachusetts General Hospital, Boston, and the session’s moderator, asked Dr. Tepper for his thoughts on how to design a good cluster headache trial. “I think we should go to the regulators and say we’re looking at the wrong outcome measure, and that we should use responder rate as the primary endpoint. That’s my guess. I think after four failed cluster studies for anti-CGRP therapies in terms of primary endpoint, all of which suggest some benefit, I think maybe we are looking at the wrong endpoint,” said Dr. Tepper.
Dr. Tepper was also asked about the potential for comparative efficacy trials testing anti-CGRP versus usual therapy, or usual therapy combined with antibodies against usual therapy. He noted that he had coauthored a recent commentary that responded to International Headache Society 2022 guidelines for randomized, placebo-controlled trials in cluster headache. “We actually did suggest comparative effectiveness [trials], both for recruitment and for compassion, but one of the problems is that verapamil is not even FDA approved for cluster headache in the US, and galcanezumab (Emgality, Eli Lilly) [is not approved] in the EU, so it becomes difficult from a regulatory standpoint to set that up, and you have to have buy in from regulatory authorities,” said Dr. Tepper.
Dr. Tepper has financial relationships with many pharmaceutical companies, including consulting for/advising Lundbeck, which funded the study. Dr. Harriott has served on the scientific advisory board of Theranica and has an authorship agreement with AbbVie.
SAN DIEGO — However, the drug met secondary outcomes of reduction in weekly attacks, mean change in baseline pain, and Patient Global Impression of Change (PGIC) score.
Eptinezumab is the latest of multiple anti–calcitonin gene-related peptide (CGRP) therapies to fail in the clinic against episodic cluster headache, all using weekly attacks as a primary endpoint, though therapies also scored positive results for secondary endpoints, according to Stewart Tepper, MD, who presented the study results at the annual meeting of the American Headache Society
Eptinezumab is already approved for migraine, and is fully bioavailable by the end of an infusion. “That was why we thought this might be a really interesting treatment for prevention of cluster headache,” said Dr. Tepper, who is VP of external research at the New England Institute for Neurology and Headache in Stamford, Connecticut.
Are We Looking at the Wrong Endpoint?
Secondary endpoints offered more encouragement. “For each week, the eptinezumab looked either numerically higher than the placebo or nominal statistical significance was achieved. By week 4, two-thirds of the patients had at least a 50% reduction in their number of weekly cluster attacks. Then the average pain intensity for the day and the patient global impression of change were all in favor of eptinezumab. That made us interested in whether we’re missing something, whether this is maybe not the correct endpoint to be looking at,” said Dr. Tepper.
He suggested that it may be time for the Food and Drug Administration (FDA) to reconsider the endpoints used in clinical trials for cluster headaches.
Study criteria included cluster periods that lasted at least 6 weeks, and at least 1 year since the diagnosis of episodic cluster headache. The study enrolled patients who were out of their cluster period, who underwent a second screening of 7-14 days after they entered a new cycle. After that, they were randomized to an injection of placebo or 400 mg eptinezumab, and followed for 4 weeks. After 4 weeks, all patients received an injection of 400 mg eptinezumab and placebo patients were crossed over to eptinezumab and followed out to 24 weeks.
The study population included 231 patients (78% male; mean age, 44 years), with a mean of 2.7 cluster headache attacks per day an average duration of 62 minutes per attack. The worst pain was reported as excruciating in 59% of participants.
The mean change in number of weekly attacks in weeks 1 and 2, compared with baseline, was not statistically significant (–4.6 with eptinezumab, –4.6 with placebo; P = .5048). More patients in the eptinezumab group had a 50% or greater reduction in attack frequency in weeks 3 (50.9% vs 37.3%; P < .05), week 3 (62.5% vs 43.8%; P < .01), and week 4 (66.7% vs 50.5%; P < .01). The difference in mean change in pain from baseline became statistically significant at week 3 and 4 (P < .01). There were also statistically significant differences in PGIC score at weeks 1, 2, and 4. The frequency of any treatment-emergent adverse event was similar in the eptinezumab and placebo groups (25.0% vs 26.5%), and only one led to treatment withdrawal in the eptinezumab group (0.9%).
Thoughts on Redesigning Cluster Headache Clinical Trials
During the Q&A session, Andrea Harriott, MD, PhD, a neurologist at Massachusetts General Hospital, Boston, and the session’s moderator, asked Dr. Tepper for his thoughts on how to design a good cluster headache trial. “I think we should go to the regulators and say we’re looking at the wrong outcome measure, and that we should use responder rate as the primary endpoint. That’s my guess. I think after four failed cluster studies for anti-CGRP therapies in terms of primary endpoint, all of which suggest some benefit, I think maybe we are looking at the wrong endpoint,” said Dr. Tepper.
Dr. Tepper was also asked about the potential for comparative efficacy trials testing anti-CGRP versus usual therapy, or usual therapy combined with antibodies against usual therapy. He noted that he had coauthored a recent commentary that responded to International Headache Society 2022 guidelines for randomized, placebo-controlled trials in cluster headache. “We actually did suggest comparative effectiveness [trials], both for recruitment and for compassion, but one of the problems is that verapamil is not even FDA approved for cluster headache in the US, and galcanezumab (Emgality, Eli Lilly) [is not approved] in the EU, so it becomes difficult from a regulatory standpoint to set that up, and you have to have buy in from regulatory authorities,” said Dr. Tepper.
Dr. Tepper has financial relationships with many pharmaceutical companies, including consulting for/advising Lundbeck, which funded the study. Dr. Harriott has served on the scientific advisory board of Theranica and has an authorship agreement with AbbVie.
SAN DIEGO — However, the drug met secondary outcomes of reduction in weekly attacks, mean change in baseline pain, and Patient Global Impression of Change (PGIC) score.
Eptinezumab is the latest of multiple anti–calcitonin gene-related peptide (CGRP) therapies to fail in the clinic against episodic cluster headache, all using weekly attacks as a primary endpoint, though therapies also scored positive results for secondary endpoints, according to Stewart Tepper, MD, who presented the study results at the annual meeting of the American Headache Society
Eptinezumab is already approved for migraine, and is fully bioavailable by the end of an infusion. “That was why we thought this might be a really interesting treatment for prevention of cluster headache,” said Dr. Tepper, who is VP of external research at the New England Institute for Neurology and Headache in Stamford, Connecticut.
Are We Looking at the Wrong Endpoint?
Secondary endpoints offered more encouragement. “For each week, the eptinezumab looked either numerically higher than the placebo or nominal statistical significance was achieved. By week 4, two-thirds of the patients had at least a 50% reduction in their number of weekly cluster attacks. Then the average pain intensity for the day and the patient global impression of change were all in favor of eptinezumab. That made us interested in whether we’re missing something, whether this is maybe not the correct endpoint to be looking at,” said Dr. Tepper.
He suggested that it may be time for the Food and Drug Administration (FDA) to reconsider the endpoints used in clinical trials for cluster headaches.
Study criteria included cluster periods that lasted at least 6 weeks, and at least 1 year since the diagnosis of episodic cluster headache. The study enrolled patients who were out of their cluster period, who underwent a second screening of 7-14 days after they entered a new cycle. After that, they were randomized to an injection of placebo or 400 mg eptinezumab, and followed for 4 weeks. After 4 weeks, all patients received an injection of 400 mg eptinezumab and placebo patients were crossed over to eptinezumab and followed out to 24 weeks.
The study population included 231 patients (78% male; mean age, 44 years), with a mean of 2.7 cluster headache attacks per day an average duration of 62 minutes per attack. The worst pain was reported as excruciating in 59% of participants.
The mean change in number of weekly attacks in weeks 1 and 2, compared with baseline, was not statistically significant (–4.6 with eptinezumab, –4.6 with placebo; P = .5048). More patients in the eptinezumab group had a 50% or greater reduction in attack frequency in weeks 3 (50.9% vs 37.3%; P < .05), week 3 (62.5% vs 43.8%; P < .01), and week 4 (66.7% vs 50.5%; P < .01). The difference in mean change in pain from baseline became statistically significant at week 3 and 4 (P < .01). There were also statistically significant differences in PGIC score at weeks 1, 2, and 4. The frequency of any treatment-emergent adverse event was similar in the eptinezumab and placebo groups (25.0% vs 26.5%), and only one led to treatment withdrawal in the eptinezumab group (0.9%).
Thoughts on Redesigning Cluster Headache Clinical Trials
During the Q&A session, Andrea Harriott, MD, PhD, a neurologist at Massachusetts General Hospital, Boston, and the session’s moderator, asked Dr. Tepper for his thoughts on how to design a good cluster headache trial. “I think we should go to the regulators and say we’re looking at the wrong outcome measure, and that we should use responder rate as the primary endpoint. That’s my guess. I think after four failed cluster studies for anti-CGRP therapies in terms of primary endpoint, all of which suggest some benefit, I think maybe we are looking at the wrong endpoint,” said Dr. Tepper.
Dr. Tepper was also asked about the potential for comparative efficacy trials testing anti-CGRP versus usual therapy, or usual therapy combined with antibodies against usual therapy. He noted that he had coauthored a recent commentary that responded to International Headache Society 2022 guidelines for randomized, placebo-controlled trials in cluster headache. “We actually did suggest comparative effectiveness [trials], both for recruitment and for compassion, but one of the problems is that verapamil is not even FDA approved for cluster headache in the US, and galcanezumab (Emgality, Eli Lilly) [is not approved] in the EU, so it becomes difficult from a regulatory standpoint to set that up, and you have to have buy in from regulatory authorities,” said Dr. Tepper.
Dr. Tepper has financial relationships with many pharmaceutical companies, including consulting for/advising Lundbeck, which funded the study. Dr. Harriott has served on the scientific advisory board of Theranica and has an authorship agreement with AbbVie.
FROM AHS 2024
Psoriatic Arthritis Symptoms Relieved with TYK2 Inhibitor in Phase 2 Trial
TOPLINE:
The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.
METHODOLOGY:
- Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
- A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
- The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.
TAKEAWAY:
- More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
- Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
- Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
- The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.
IN PRACTICE:
“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
SOURCE:
Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.
LIMITATIONS:
The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
DISCLOSURES:
The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.
METHODOLOGY:
- Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
- A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
- The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.
TAKEAWAY:
- More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
- Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
- Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
- The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.
IN PRACTICE:
“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
SOURCE:
Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.
LIMITATIONS:
The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
DISCLOSURES:
The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
The tyrosine kinase 2 (TYK2) inhibitor TAK-279 demonstrated superiority to placebo in patients with active psoriatic arthritis (PsA), according to phase 2 trial results.
METHODOLOGY:
- Eligible patients were over 18 years old, had PsA for over 6 months, met the classification criteria for PsA, and had at least three swollen and tender joints despite prior nonsteroidal anti-inflammatory drug, disease-modifying antirheumatic drug, or biologic treatment.
- A total of 290 patients were randomized 1:1:1:1 to receive placebo, oral TAK-279 5 mg, 15 mg, or 30 mg once daily.
- The primary endpoint was a 20% improvement in the American College of Rheumatology response criteria (ACR20) at 12 weeks.
TAKEAWAY:
- More than half of patients assigned to TAK-279 15 mg (53.3%) and TAK-279 30 mg (54.2%) achieved ACR20 at 12 weeks, compared with 29.2% of those assigned to placebo.
- Psoriasis Area and Severity Index 75 response rates were also higher in patients assigned to TAK-279 30 mg (45.7%) or 15 mg (28.3%) than those in placebo (15.4%).
- Treatment-emergent adverse events (TEAEs) of any kind were numerically higher in the 30-mg group, though serious TEAEs were similar across all treatment arms.
- The most frequent adverse events were nasal pharyngitis, upper respiratory tract infections, headache, and rash, with rash being most common in the TAK-279 30-mg group.
IN PRACTICE:
“There are few targeted oral therapies for active PSA available currently,” said lead author Alan Kivitz, MD, Altoona Center for Clinical Research, Duncansville, Pennsylvania, “and [TAK-279], which was well tolerated and demonstrated superior efficacy versus placebo, may be a promising targeted oral therapy for patients with PsA.”
SOURCE:
Dr. Kivitz presented the study findings at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting, held in Vienna.
LIMITATIONS:
The study was a phase 2 trial, and larger studies in active PsA are needed (and currently being planned).
DISCLOSURES:
The phase 2 trial was funded by Nimbus and Takeda. Dr. Kivitz has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Pfizer, and UCB. He has stock or stock options in Pfizer, Amgen, GlaxoSmithKline, Gilead, Novartis, and Pfizer and has received consultant fees from Fresenius Kabi, Genzyme, Gilead, Grunenthal, GlaxoSmithKline, Horizon, Janssen, Pfizer, Selecta, SynAct Pharma, and Takeda. He has been part of a board or advisory board for ChemoCentryx, Horizon, Janssen, Novartis, Princeton Biopartners, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
Psoriatic Arthritis Drug Candidate Sonelokimab Yields Significant Improvements in Phase 2 Trial
TOPLINE:
Treatment of patients with active psoriatic arthritis with sonelokimab — an interleukin (IL)-17A- and IL-17F-inhibiting nanobody — led to a higher percentage of patients with 50% or greater improvement in American College of Rheumatology response criteria (ACR50) compared with the placebo in a phase 2 trial.
METHODOLOGY:
- Sonelokimab is a 40-kDa nanobody that binds to IL-17A, IL-17F, and albumin.
- Eligible patients were at least 18 years old with active PsA (at least three swollen and three tender joints) and had a psoriasis diagnosis.
- A total of 207 patients were randomized 1:1:1:1 to every 4 weeks receive placebo, sonelokimab 60 mg with no induction (NI) period, sonelokimab 60 mg with induction, and sonelokimab 120 mg with induction.
- Induction was once every 2 weeks up to week 8 of the trial.
- The primary endpoint was meeting ACR20 response criteria at 12 weeks.
TAKEAWAY:
- About 46% of patients in the sonelokimab 120-mg and 60-mg groups achieved ACR50, compared with 36.6% in the sonelokimab 60-mg NI group and 20% of those assigned to placebo.
- ACR20 and 90% or greater reduction in Psoriasis Area and Severity Index score response rates were higher in all three sonelokimab groups than in the placebo group.
- There were no unexpected safety findings during the trial, and no cases of inflammatory bowel disease or major cardiovascular events.
- There were two cases of oral candidiasis, which did not lead to study discontinuation.
IN PRACTICE:
These data “support further exploration in phase 3 trials of sonelokimab to evaluate its potential for the treatment of PsA,” the authors noted in the presentation.
SOURCE:
Iain B. McInnes, MD, PhD, of the University of Glasgow, Glasgow, Scotland, presented these phase 2 trial results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Congress, held in Vienna.
LIMITATIONS:
The results are from a phase 2 trial, and more research is needed.
DISCLOSURES:
MoonLake Immunotherapeutics funded the research. Dr. McInnes disclosed relationships with AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Evelo, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
Treatment of patients with active psoriatic arthritis with sonelokimab — an interleukin (IL)-17A- and IL-17F-inhibiting nanobody — led to a higher percentage of patients with 50% or greater improvement in American College of Rheumatology response criteria (ACR50) compared with the placebo in a phase 2 trial.
METHODOLOGY:
- Sonelokimab is a 40-kDa nanobody that binds to IL-17A, IL-17F, and albumin.
- Eligible patients were at least 18 years old with active PsA (at least three swollen and three tender joints) and had a psoriasis diagnosis.
- A total of 207 patients were randomized 1:1:1:1 to every 4 weeks receive placebo, sonelokimab 60 mg with no induction (NI) period, sonelokimab 60 mg with induction, and sonelokimab 120 mg with induction.
- Induction was once every 2 weeks up to week 8 of the trial.
- The primary endpoint was meeting ACR20 response criteria at 12 weeks.
TAKEAWAY:
- About 46% of patients in the sonelokimab 120-mg and 60-mg groups achieved ACR50, compared with 36.6% in the sonelokimab 60-mg NI group and 20% of those assigned to placebo.
- ACR20 and 90% or greater reduction in Psoriasis Area and Severity Index score response rates were higher in all three sonelokimab groups than in the placebo group.
- There were no unexpected safety findings during the trial, and no cases of inflammatory bowel disease or major cardiovascular events.
- There were two cases of oral candidiasis, which did not lead to study discontinuation.
IN PRACTICE:
These data “support further exploration in phase 3 trials of sonelokimab to evaluate its potential for the treatment of PsA,” the authors noted in the presentation.
SOURCE:
Iain B. McInnes, MD, PhD, of the University of Glasgow, Glasgow, Scotland, presented these phase 2 trial results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Congress, held in Vienna.
LIMITATIONS:
The results are from a phase 2 trial, and more research is needed.
DISCLOSURES:
MoonLake Immunotherapeutics funded the research. Dr. McInnes disclosed relationships with AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Evelo, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
TOPLINE:
Treatment of patients with active psoriatic arthritis with sonelokimab — an interleukin (IL)-17A- and IL-17F-inhibiting nanobody — led to a higher percentage of patients with 50% or greater improvement in American College of Rheumatology response criteria (ACR50) compared with the placebo in a phase 2 trial.
METHODOLOGY:
- Sonelokimab is a 40-kDa nanobody that binds to IL-17A, IL-17F, and albumin.
- Eligible patients were at least 18 years old with active PsA (at least three swollen and three tender joints) and had a psoriasis diagnosis.
- A total of 207 patients were randomized 1:1:1:1 to every 4 weeks receive placebo, sonelokimab 60 mg with no induction (NI) period, sonelokimab 60 mg with induction, and sonelokimab 120 mg with induction.
- Induction was once every 2 weeks up to week 8 of the trial.
- The primary endpoint was meeting ACR20 response criteria at 12 weeks.
TAKEAWAY:
- About 46% of patients in the sonelokimab 120-mg and 60-mg groups achieved ACR50, compared with 36.6% in the sonelokimab 60-mg NI group and 20% of those assigned to placebo.
- ACR20 and 90% or greater reduction in Psoriasis Area and Severity Index score response rates were higher in all three sonelokimab groups than in the placebo group.
- There were no unexpected safety findings during the trial, and no cases of inflammatory bowel disease or major cardiovascular events.
- There were two cases of oral candidiasis, which did not lead to study discontinuation.
IN PRACTICE:
These data “support further exploration in phase 3 trials of sonelokimab to evaluate its potential for the treatment of PsA,” the authors noted in the presentation.
SOURCE:
Iain B. McInnes, MD, PhD, of the University of Glasgow, Glasgow, Scotland, presented these phase 2 trial results at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Congress, held in Vienna.
LIMITATIONS:
The results are from a phase 2 trial, and more research is needed.
DISCLOSURES:
MoonLake Immunotherapeutics funded the research. Dr. McInnes disclosed relationships with AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Causeway Therapeutics, Cabaletta Bio, Compugen, Evelo, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, and UCB. Other authors also disclosed many relationships with pharmaceutical companies.
A version of this article first appeared on Medscape.com.
Patient-Driven Care Plus Telemonitoring Yields Promising Results for Spondyloarthritis
VIENNA — People with spondyloarthritis (SpA) who have low or stable disease activity can effectively and safely be managed using a model of patient-initiated care with or without remote monitoring, suggested the results of two separate trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.
In the 18-month, single-center ReMonit study that included 243 people with axial SpA (axSpA), patient-initiated care was found to be noninferior for keeping them in a low-disease activity state, compared with both usual hospital follow-up and remote digital monitoring.
Meanwhile, in the 12-month, multicenter TeleSpA study, which included 200 patients with any type of SpA, the number of hospital visits needed by people who were randomly assigned to receive patient-initiated care together with asynchronous telemonitoring was significantly lower than for the usual-care group, with no detriment to the participants’ overall health outcomes or safety. Moreover, the strategy was deemed cost-effective from a healthcare provision perspective.
Time to Rationalize Healthcare Resources?
People with chronic rheumatic diseases such as axSpA require long-term follow-up in specialist healthcare centers, Inger Jorid Berg, MD, PhD, of Diakonhjemmet Hospital in Oslo, Norway, said when she presented the findings of the ReMonit study as a late-breaking abstract.
“Traditionally, this has been offered as prescheduled face-to-face consultations at an outpatient clinic, but remote monitoring and patient-initiated care may allow for more targeted and efficient uses of healthcare resources,” Dr. Berg said.
“The end goal of what you’re trying to do is increase the efficiency of outpatient care and provide more patient-tailored care,” Kasper Hermans, MD, said in an interview. He presented the results of the TeleSpA study.
Dr. Hermans, who is a rheumatology fellow and PhD candidate at Maastricht University, Maastricht, the Netherlands, observed during his presentation at EULAR 2024 that there is an increasing demand for rheumatology services but an expected shortfall in the future workforce. Thus, “sustainable alternative strategies are needed for optimizing the efficiency of care,” he said.
People need to have timely access to care, Dr. Hermans stressed, but perhaps alternatives to the traditional models of care where patients are seen routinely every 6 or 12 months are needed, particularly as prior work had suggested that around one-third of people who were seen by a rheumatologist perhaps did not need to be.
A strategy of patient-initiated care — which is where people are seen by a healthcare provider only if they feel that they need to and request a consultation — is therefore an attractive proposition, particularly if it is backed up with remote monitoring, which is what the TeleSpA study was testing.
Two Distinct Studies
ReMonit and TeleSpA were two distinct studies. While both were noninferiority trials and involved patient-initiated care and telemonitoring of outpatients with SpA, that is where the similarities generally end.
Notably, ReMonit included a very specific population of patients — all had a diagnosis of axSpA and were being treated with a tumor necrosis factor (TNF) inhibitor and had been on a stable dose for the last 6 months. For inclusion, they also had to have inactive disease or low disease activity, as indicated by an Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1.
ReMonit’s telemonitoring strategy involved participants completing monthly questionnaires using the Dignio smartphone app. Patients first completed the Patient Global Assessment (PGA) and noted whether they had experienced a flare in their disease. If they had a flare or their PGA score was 3 or higher, then they were asked to also complete the Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI). If the BASDAI score was 4 or more, then the patient was called by a study nurse and offered a consultation.
“Patients in all three groups were recommended to take blood samples at the general practitioner’s or at the hospital every third month as a safety procedure when using TNF inhibitors,” Dr. Berg said.
The primary outcome was the proportion of people who remained with low disease activity (ASDAS < 2.1) at 6, 12, and 18 months in each of the three arms of the trial, which were patient-initiated care (n = 81), monthly remote monitoring (n = 80), or usual follow-up in the hospital every 6 months (n = 82).
TeleSpA on the other hand was a “much more pragmatic trial, much closer to actual care,” Dr. Hermans said. “We included axial spondyloarthritis, peripheral spondyloarthritis, or patients who had both axial and peripheral disease, including patients with psoriatic arthritis,” he said, adding that their inclusion was regardless of their baseline ASDAS based on C-reactive protein (ASDAS-CRP).
This means that patients who would otherwise have been classified at baseline as having high disease activity (by ASDAS-CRP or similar disease activity measures) could be included. The main proviso was that both the patient and their rheumatologist had to define the condition as being stable with an acceptable level of symptom control and no immediate plans to change treatment within the next 3 months.
TeleSpA’s remote monitoring strategy involved the use of SpA-Net, which Dr. Hermans and coinvestigators have described previously as “an ongoing, disease-specific, prospective, web-based registry for monitoring SpA in daily practice.” This captures a host of clinical and laboratory test information.
SpA-Net was used in both arms of the study. However, while the 100 participants in the standard-care arm completed questionnaires and had tests before every in-person visit that had been prescheduled with their rheumatologist, the 100 individuals in the patient-initiated care arm had no prescheduled in-person visits except for being seen at the start and end of the study. These patients were reminded via email to complete the necessary SpA-Net registry questionnaires at 6 months.
The primary outcome for TeleSpA was the total number of rheumatology visits, including both physical and telephone or video consultations, within a 1-year period.
ReMonit Results
Berg reported that similar percentages of patients remained in a low disease activity state at 6, 12, and 18 months, regardless of the group that they had been randomized into, and that there was little change seen within the individual groups.
For instance, at 6, 12, and 18 months, 92%, 91%, and 92% of individuals in the patient-initiated arm had an ASDAS of < 2.1. Corresponding percentages for the usual-care arm were 96%, 93%, and 90% and for the remote-monitoring arm were 96%, 96%, and 94%.
Both patient-initiated care and remote monitoring were noninferior to usual care, and patient-initiated care was also noninferior to remote monitoring. There were no differences between the trial arms in terms of disease activity, measured using either ASDAS or BASDAI, at 6, 12, or 18 months.
Dr. Berg stated that “patient satisfaction was high in all three follow-up strategies, and there was the lowest resource use with patient-initiated care.” She concluded that “remote monitoring and patient-initiated care could be implemented in the follow-up of patients with axial spondyloarthritis and low disease activity.”
TeleSpA Results
In TeleSpA, people in the patient-initiated care and telemonitoring arm were seen a mean of 1.9 times over the course of the 1-year follow-up vs 2.6 for people in the usual care arm. The reduction was caused in part by the decrease in physical visits (1.4 vs 2.0) as there were the same mean number of telephone visits in each group. Overall, there was a 25.4% reduction in consultations comparing the patient-initiated care and telemonitoring arm with the usual-care arm.
Importantly, the intervention was noninferior regarding all of the predefined health outcomes: ASDAS, BASDAI, pain assessed using a visual analog scale, patient global assessment, and physician global assessment.
And more than 90% of participants in both groups reported having an overall good experience with their care.
Dr. Hermans noted after his presentation that an additional study had been performed where “we actively engaged with patients in the intervention group as well as healthcare providers to ask them what their experiences were with the intervention, how we could possibly improve it, and whether or not they thought that it was a valid approach to follow-up after the end of the study. And results were very, very reassuring.”
In terms of safety, eight serious adverse events were reported, but none were related to the study intervention, Dr. Hermans said.
Dr. Hermans reported that there was “negligible difference” in the 1-year quality-adjusted life-years (+0.004, in favor of the intervention overall) and that, while healthcare costs were lower at €243/year for the entire intervention period, societal costs were higher, at €513/year vs usual care. The latter was thought to be “due to an unexpected rise in absenteeism that we think was most likely due to a small amount of outliers,” Dr. Hermans said.
Nonetheless, using at willingness-to-pay threshold of €20,000/ quality-adjusted life year, he reported that the added value of patient-initiated care with remote monitoring yielded a potential net monetary benefit of +€322 from a healthcare perspective for the entire intervention period.
“We believe that these results support the fast-paced adoption of remote care interventions,” Dr. Hermans said. “In the context that I described earlier, of decreasing healthcare personnel and rising costs, we believe that this could be a valuable approach for follow-up for patients with stable axSpA.”
ReMonit was sponsored by Diakonhjemmet Hospital, and TeleSpA was sponsored by Maastricht University Medical Center, with funding from the Dutch Arthritis Society. Dr. Berg and Dr. Hermans had no relevant conflicts of interest to report.
A version of this article first appeared on Medscape.com.
Editor’s Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
VIENNA — People with spondyloarthritis (SpA) who have low or stable disease activity can effectively and safely be managed using a model of patient-initiated care with or without remote monitoring, suggested the results of two separate trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.
In the 18-month, single-center ReMonit study that included 243 people with axial SpA (axSpA), patient-initiated care was found to be noninferior for keeping them in a low-disease activity state, compared with both usual hospital follow-up and remote digital monitoring.
Meanwhile, in the 12-month, multicenter TeleSpA study, which included 200 patients with any type of SpA, the number of hospital visits needed by people who were randomly assigned to receive patient-initiated care together with asynchronous telemonitoring was significantly lower than for the usual-care group, with no detriment to the participants’ overall health outcomes or safety. Moreover, the strategy was deemed cost-effective from a healthcare provision perspective.
Time to Rationalize Healthcare Resources?
People with chronic rheumatic diseases such as axSpA require long-term follow-up in specialist healthcare centers, Inger Jorid Berg, MD, PhD, of Diakonhjemmet Hospital in Oslo, Norway, said when she presented the findings of the ReMonit study as a late-breaking abstract.
“Traditionally, this has been offered as prescheduled face-to-face consultations at an outpatient clinic, but remote monitoring and patient-initiated care may allow for more targeted and efficient uses of healthcare resources,” Dr. Berg said.
“The end goal of what you’re trying to do is increase the efficiency of outpatient care and provide more patient-tailored care,” Kasper Hermans, MD, said in an interview. He presented the results of the TeleSpA study.
Dr. Hermans, who is a rheumatology fellow and PhD candidate at Maastricht University, Maastricht, the Netherlands, observed during his presentation at EULAR 2024 that there is an increasing demand for rheumatology services but an expected shortfall in the future workforce. Thus, “sustainable alternative strategies are needed for optimizing the efficiency of care,” he said.
People need to have timely access to care, Dr. Hermans stressed, but perhaps alternatives to the traditional models of care where patients are seen routinely every 6 or 12 months are needed, particularly as prior work had suggested that around one-third of people who were seen by a rheumatologist perhaps did not need to be.
A strategy of patient-initiated care — which is where people are seen by a healthcare provider only if they feel that they need to and request a consultation — is therefore an attractive proposition, particularly if it is backed up with remote monitoring, which is what the TeleSpA study was testing.
Two Distinct Studies
ReMonit and TeleSpA were two distinct studies. While both were noninferiority trials and involved patient-initiated care and telemonitoring of outpatients with SpA, that is where the similarities generally end.
Notably, ReMonit included a very specific population of patients — all had a diagnosis of axSpA and were being treated with a tumor necrosis factor (TNF) inhibitor and had been on a stable dose for the last 6 months. For inclusion, they also had to have inactive disease or low disease activity, as indicated by an Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1.
ReMonit’s telemonitoring strategy involved participants completing monthly questionnaires using the Dignio smartphone app. Patients first completed the Patient Global Assessment (PGA) and noted whether they had experienced a flare in their disease. If they had a flare or their PGA score was 3 or higher, then they were asked to also complete the Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI). If the BASDAI score was 4 or more, then the patient was called by a study nurse and offered a consultation.
“Patients in all three groups were recommended to take blood samples at the general practitioner’s or at the hospital every third month as a safety procedure when using TNF inhibitors,” Dr. Berg said.
The primary outcome was the proportion of people who remained with low disease activity (ASDAS < 2.1) at 6, 12, and 18 months in each of the three arms of the trial, which were patient-initiated care (n = 81), monthly remote monitoring (n = 80), or usual follow-up in the hospital every 6 months (n = 82).
TeleSpA on the other hand was a “much more pragmatic trial, much closer to actual care,” Dr. Hermans said. “We included axial spondyloarthritis, peripheral spondyloarthritis, or patients who had both axial and peripheral disease, including patients with psoriatic arthritis,” he said, adding that their inclusion was regardless of their baseline ASDAS based on C-reactive protein (ASDAS-CRP).
This means that patients who would otherwise have been classified at baseline as having high disease activity (by ASDAS-CRP or similar disease activity measures) could be included. The main proviso was that both the patient and their rheumatologist had to define the condition as being stable with an acceptable level of symptom control and no immediate plans to change treatment within the next 3 months.
TeleSpA’s remote monitoring strategy involved the use of SpA-Net, which Dr. Hermans and coinvestigators have described previously as “an ongoing, disease-specific, prospective, web-based registry for monitoring SpA in daily practice.” This captures a host of clinical and laboratory test information.
SpA-Net was used in both arms of the study. However, while the 100 participants in the standard-care arm completed questionnaires and had tests before every in-person visit that had been prescheduled with their rheumatologist, the 100 individuals in the patient-initiated care arm had no prescheduled in-person visits except for being seen at the start and end of the study. These patients were reminded via email to complete the necessary SpA-Net registry questionnaires at 6 months.
The primary outcome for TeleSpA was the total number of rheumatology visits, including both physical and telephone or video consultations, within a 1-year period.
ReMonit Results
Berg reported that similar percentages of patients remained in a low disease activity state at 6, 12, and 18 months, regardless of the group that they had been randomized into, and that there was little change seen within the individual groups.
For instance, at 6, 12, and 18 months, 92%, 91%, and 92% of individuals in the patient-initiated arm had an ASDAS of < 2.1. Corresponding percentages for the usual-care arm were 96%, 93%, and 90% and for the remote-monitoring arm were 96%, 96%, and 94%.
Both patient-initiated care and remote monitoring were noninferior to usual care, and patient-initiated care was also noninferior to remote monitoring. There were no differences between the trial arms in terms of disease activity, measured using either ASDAS or BASDAI, at 6, 12, or 18 months.
Dr. Berg stated that “patient satisfaction was high in all three follow-up strategies, and there was the lowest resource use with patient-initiated care.” She concluded that “remote monitoring and patient-initiated care could be implemented in the follow-up of patients with axial spondyloarthritis and low disease activity.”
TeleSpA Results
In TeleSpA, people in the patient-initiated care and telemonitoring arm were seen a mean of 1.9 times over the course of the 1-year follow-up vs 2.6 for people in the usual care arm. The reduction was caused in part by the decrease in physical visits (1.4 vs 2.0) as there were the same mean number of telephone visits in each group. Overall, there was a 25.4% reduction in consultations comparing the patient-initiated care and telemonitoring arm with the usual-care arm.
Importantly, the intervention was noninferior regarding all of the predefined health outcomes: ASDAS, BASDAI, pain assessed using a visual analog scale, patient global assessment, and physician global assessment.
And more than 90% of participants in both groups reported having an overall good experience with their care.
Dr. Hermans noted after his presentation that an additional study had been performed where “we actively engaged with patients in the intervention group as well as healthcare providers to ask them what their experiences were with the intervention, how we could possibly improve it, and whether or not they thought that it was a valid approach to follow-up after the end of the study. And results were very, very reassuring.”
In terms of safety, eight serious adverse events were reported, but none were related to the study intervention, Dr. Hermans said.
Dr. Hermans reported that there was “negligible difference” in the 1-year quality-adjusted life-years (+0.004, in favor of the intervention overall) and that, while healthcare costs were lower at €243/year for the entire intervention period, societal costs were higher, at €513/year vs usual care. The latter was thought to be “due to an unexpected rise in absenteeism that we think was most likely due to a small amount of outliers,” Dr. Hermans said.
Nonetheless, using at willingness-to-pay threshold of €20,000/ quality-adjusted life year, he reported that the added value of patient-initiated care with remote monitoring yielded a potential net monetary benefit of +€322 from a healthcare perspective for the entire intervention period.
“We believe that these results support the fast-paced adoption of remote care interventions,” Dr. Hermans said. “In the context that I described earlier, of decreasing healthcare personnel and rising costs, we believe that this could be a valuable approach for follow-up for patients with stable axSpA.”
ReMonit was sponsored by Diakonhjemmet Hospital, and TeleSpA was sponsored by Maastricht University Medical Center, with funding from the Dutch Arthritis Society. Dr. Berg and Dr. Hermans had no relevant conflicts of interest to report.
A version of this article first appeared on Medscape.com.
Editor’s Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
VIENNA — People with spondyloarthritis (SpA) who have low or stable disease activity can effectively and safely be managed using a model of patient-initiated care with or without remote monitoring, suggested the results of two separate trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2024 Annual Meeting.
In the 18-month, single-center ReMonit study that included 243 people with axial SpA (axSpA), patient-initiated care was found to be noninferior for keeping them in a low-disease activity state, compared with both usual hospital follow-up and remote digital monitoring.
Meanwhile, in the 12-month, multicenter TeleSpA study, which included 200 patients with any type of SpA, the number of hospital visits needed by people who were randomly assigned to receive patient-initiated care together with asynchronous telemonitoring was significantly lower than for the usual-care group, with no detriment to the participants’ overall health outcomes or safety. Moreover, the strategy was deemed cost-effective from a healthcare provision perspective.
Time to Rationalize Healthcare Resources?
People with chronic rheumatic diseases such as axSpA require long-term follow-up in specialist healthcare centers, Inger Jorid Berg, MD, PhD, of Diakonhjemmet Hospital in Oslo, Norway, said when she presented the findings of the ReMonit study as a late-breaking abstract.
“Traditionally, this has been offered as prescheduled face-to-face consultations at an outpatient clinic, but remote monitoring and patient-initiated care may allow for more targeted and efficient uses of healthcare resources,” Dr. Berg said.
“The end goal of what you’re trying to do is increase the efficiency of outpatient care and provide more patient-tailored care,” Kasper Hermans, MD, said in an interview. He presented the results of the TeleSpA study.
Dr. Hermans, who is a rheumatology fellow and PhD candidate at Maastricht University, Maastricht, the Netherlands, observed during his presentation at EULAR 2024 that there is an increasing demand for rheumatology services but an expected shortfall in the future workforce. Thus, “sustainable alternative strategies are needed for optimizing the efficiency of care,” he said.
People need to have timely access to care, Dr. Hermans stressed, but perhaps alternatives to the traditional models of care where patients are seen routinely every 6 or 12 months are needed, particularly as prior work had suggested that around one-third of people who were seen by a rheumatologist perhaps did not need to be.
A strategy of patient-initiated care — which is where people are seen by a healthcare provider only if they feel that they need to and request a consultation — is therefore an attractive proposition, particularly if it is backed up with remote monitoring, which is what the TeleSpA study was testing.
Two Distinct Studies
ReMonit and TeleSpA were two distinct studies. While both were noninferiority trials and involved patient-initiated care and telemonitoring of outpatients with SpA, that is where the similarities generally end.
Notably, ReMonit included a very specific population of patients — all had a diagnosis of axSpA and were being treated with a tumor necrosis factor (TNF) inhibitor and had been on a stable dose for the last 6 months. For inclusion, they also had to have inactive disease or low disease activity, as indicated by an Ankylosing Spondylitis Disease Activity Score (ASDAS) < 2.1.
ReMonit’s telemonitoring strategy involved participants completing monthly questionnaires using the Dignio smartphone app. Patients first completed the Patient Global Assessment (PGA) and noted whether they had experienced a flare in their disease. If they had a flare or their PGA score was 3 or higher, then they were asked to also complete the Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI). If the BASDAI score was 4 or more, then the patient was called by a study nurse and offered a consultation.
“Patients in all three groups were recommended to take blood samples at the general practitioner’s or at the hospital every third month as a safety procedure when using TNF inhibitors,” Dr. Berg said.
The primary outcome was the proportion of people who remained with low disease activity (ASDAS < 2.1) at 6, 12, and 18 months in each of the three arms of the trial, which were patient-initiated care (n = 81), monthly remote monitoring (n = 80), or usual follow-up in the hospital every 6 months (n = 82).
TeleSpA on the other hand was a “much more pragmatic trial, much closer to actual care,” Dr. Hermans said. “We included axial spondyloarthritis, peripheral spondyloarthritis, or patients who had both axial and peripheral disease, including patients with psoriatic arthritis,” he said, adding that their inclusion was regardless of their baseline ASDAS based on C-reactive protein (ASDAS-CRP).
This means that patients who would otherwise have been classified at baseline as having high disease activity (by ASDAS-CRP or similar disease activity measures) could be included. The main proviso was that both the patient and their rheumatologist had to define the condition as being stable with an acceptable level of symptom control and no immediate plans to change treatment within the next 3 months.
TeleSpA’s remote monitoring strategy involved the use of SpA-Net, which Dr. Hermans and coinvestigators have described previously as “an ongoing, disease-specific, prospective, web-based registry for monitoring SpA in daily practice.” This captures a host of clinical and laboratory test information.
SpA-Net was used in both arms of the study. However, while the 100 participants in the standard-care arm completed questionnaires and had tests before every in-person visit that had been prescheduled with their rheumatologist, the 100 individuals in the patient-initiated care arm had no prescheduled in-person visits except for being seen at the start and end of the study. These patients were reminded via email to complete the necessary SpA-Net registry questionnaires at 6 months.
The primary outcome for TeleSpA was the total number of rheumatology visits, including both physical and telephone or video consultations, within a 1-year period.
ReMonit Results
Berg reported that similar percentages of patients remained in a low disease activity state at 6, 12, and 18 months, regardless of the group that they had been randomized into, and that there was little change seen within the individual groups.
For instance, at 6, 12, and 18 months, 92%, 91%, and 92% of individuals in the patient-initiated arm had an ASDAS of < 2.1. Corresponding percentages for the usual-care arm were 96%, 93%, and 90% and for the remote-monitoring arm were 96%, 96%, and 94%.
Both patient-initiated care and remote monitoring were noninferior to usual care, and patient-initiated care was also noninferior to remote monitoring. There were no differences between the trial arms in terms of disease activity, measured using either ASDAS or BASDAI, at 6, 12, or 18 months.
Dr. Berg stated that “patient satisfaction was high in all three follow-up strategies, and there was the lowest resource use with patient-initiated care.” She concluded that “remote monitoring and patient-initiated care could be implemented in the follow-up of patients with axial spondyloarthritis and low disease activity.”
TeleSpA Results
In TeleSpA, people in the patient-initiated care and telemonitoring arm were seen a mean of 1.9 times over the course of the 1-year follow-up vs 2.6 for people in the usual care arm. The reduction was caused in part by the decrease in physical visits (1.4 vs 2.0) as there were the same mean number of telephone visits in each group. Overall, there was a 25.4% reduction in consultations comparing the patient-initiated care and telemonitoring arm with the usual-care arm.
Importantly, the intervention was noninferior regarding all of the predefined health outcomes: ASDAS, BASDAI, pain assessed using a visual analog scale, patient global assessment, and physician global assessment.
And more than 90% of participants in both groups reported having an overall good experience with their care.
Dr. Hermans noted after his presentation that an additional study had been performed where “we actively engaged with patients in the intervention group as well as healthcare providers to ask them what their experiences were with the intervention, how we could possibly improve it, and whether or not they thought that it was a valid approach to follow-up after the end of the study. And results were very, very reassuring.”
In terms of safety, eight serious adverse events were reported, but none were related to the study intervention, Dr. Hermans said.
Dr. Hermans reported that there was “negligible difference” in the 1-year quality-adjusted life-years (+0.004, in favor of the intervention overall) and that, while healthcare costs were lower at €243/year for the entire intervention period, societal costs were higher, at €513/year vs usual care. The latter was thought to be “due to an unexpected rise in absenteeism that we think was most likely due to a small amount of outliers,” Dr. Hermans said.
Nonetheless, using at willingness-to-pay threshold of €20,000/ quality-adjusted life year, he reported that the added value of patient-initiated care with remote monitoring yielded a potential net monetary benefit of +€322 from a healthcare perspective for the entire intervention period.
“We believe that these results support the fast-paced adoption of remote care interventions,” Dr. Hermans said. “In the context that I described earlier, of decreasing healthcare personnel and rising costs, we believe that this could be a valuable approach for follow-up for patients with stable axSpA.”
ReMonit was sponsored by Diakonhjemmet Hospital, and TeleSpA was sponsored by Maastricht University Medical Center, with funding from the Dutch Arthritis Society. Dr. Berg and Dr. Hermans had no relevant conflicts of interest to report.
A version of this article first appeared on Medscape.com.
Editor’s Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
FROM EULAR 2024
B-ALL: New Findings Confirm Efficacy of CAR T Product
These findings also highlight the favorable impact of CAR T persistence on treatment outcomes, and suggest that consolidative stem cell transplant (SCT) in R/R B-ALL patients treated with obe-cel does not improve outcomes, Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.
The overall complete remission or complete remission with incomplete count recovery rate was 78% among 127 patients enrolled in the open-label, single-arm study and infused with obe-cel. Among the 99 patients who responded, 18 proceeded to consolidative SCT while in remission, Dr. Jabbour said, noting that all 18 who received SCT were in minimal residual disease (MRD)–negative remission at the time of transplant.
Of those 18 patients, 10 had ongoing CAR T persistence prior to transplant, he said.
At median follow-up of 21.5 months, 40% of responders were in ongoing remission without the need for subsequent consolidation with SCT or other therapy, whereas SCT did not appear to improve outcomes.
The median event-free survival (EFS) after censoring for transplant was 11.9 months, and the 12-month EFS rate was 49.5%. Without censoring for transplant, the EFS and 12-month EFS rate were 9.0 months and 44%, respectively.
“I would like to highlight that the time to transplant was 100 days, and of those 18 patients, all in MRD-negative status ... 80% relapsed or died from transplant-related complications,” Dr. Jabbour said.
Median overall survival (OS) without censoring for transplant was 15.6 months, and the 12-month OS rate was 61.1%. After censoring for transplant, the median OS and 12-month OS rate 23.8 months 63.7%, respectively. The survival curves were fully overlapping, indicating that transplant did not improve OS outcomes.
“Furthermore, when you look at the EFS and [OS], both show a potential plateau for a long-term outcome, and this trend is similar to what was reported in a phase 1 trial with 2 years of follow up and more,” Dr. Jabbour said.
The investigators also assessed the impact of loss of CAR T-cell persistence and loss of B-cell aplasia and found that “both ongoing CAR T-cell persistence and ongoing B-cell aplasia, were correlated with better event-free survival,” he noted, explaining that the risk of relapse was 2.7 times greater in those who lost versus maintained CAR T-cell persistence, and 1.7 times greater in those who lost versus maintained B-cell aplasia.
Among those with ongoing remission at 6 months, median EFS was 15.1 months in those who lost CAR T-cell persistence, whereas the median EFS was not reached in those who maintained CAR T-cell persistence.
Obe-cel is an autologous CAR T-cell product with a fast off-rate CD19 binder designed to mitigate immunotoxicity and improve CAR T-cell expansion and persistence, Dr. Jabbour said, noting that pooled efficacy and safety results from the FELIX phase 1b and 2 trials of heavily pretreated patients have previously been reported.
The findings support the use of obe-cel as a standard treatment in this patient population, and demonstrate that ongoing CAR T-cell persistence and B-cell aplasia are associated with improved EFS — without further consolidation therapy after treatment, he concluded.
This study was funded by Autolus Therapeutics. Dr. Jabbour disclosed ties with Abbvie, Ascentage Pharma, Adaptive Biotechnologies, Amgen, Astellas Pharma, Bristol-Myers Squibb, Genentech, Incyte, Pfizer, and Takeda.
These findings also highlight the favorable impact of CAR T persistence on treatment outcomes, and suggest that consolidative stem cell transplant (SCT) in R/R B-ALL patients treated with obe-cel does not improve outcomes, Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.
The overall complete remission or complete remission with incomplete count recovery rate was 78% among 127 patients enrolled in the open-label, single-arm study and infused with obe-cel. Among the 99 patients who responded, 18 proceeded to consolidative SCT while in remission, Dr. Jabbour said, noting that all 18 who received SCT were in minimal residual disease (MRD)–negative remission at the time of transplant.
Of those 18 patients, 10 had ongoing CAR T persistence prior to transplant, he said.
At median follow-up of 21.5 months, 40% of responders were in ongoing remission without the need for subsequent consolidation with SCT or other therapy, whereas SCT did not appear to improve outcomes.
The median event-free survival (EFS) after censoring for transplant was 11.9 months, and the 12-month EFS rate was 49.5%. Without censoring for transplant, the EFS and 12-month EFS rate were 9.0 months and 44%, respectively.
“I would like to highlight that the time to transplant was 100 days, and of those 18 patients, all in MRD-negative status ... 80% relapsed or died from transplant-related complications,” Dr. Jabbour said.
Median overall survival (OS) without censoring for transplant was 15.6 months, and the 12-month OS rate was 61.1%. After censoring for transplant, the median OS and 12-month OS rate 23.8 months 63.7%, respectively. The survival curves were fully overlapping, indicating that transplant did not improve OS outcomes.
“Furthermore, when you look at the EFS and [OS], both show a potential plateau for a long-term outcome, and this trend is similar to what was reported in a phase 1 trial with 2 years of follow up and more,” Dr. Jabbour said.
The investigators also assessed the impact of loss of CAR T-cell persistence and loss of B-cell aplasia and found that “both ongoing CAR T-cell persistence and ongoing B-cell aplasia, were correlated with better event-free survival,” he noted, explaining that the risk of relapse was 2.7 times greater in those who lost versus maintained CAR T-cell persistence, and 1.7 times greater in those who lost versus maintained B-cell aplasia.
Among those with ongoing remission at 6 months, median EFS was 15.1 months in those who lost CAR T-cell persistence, whereas the median EFS was not reached in those who maintained CAR T-cell persistence.
Obe-cel is an autologous CAR T-cell product with a fast off-rate CD19 binder designed to mitigate immunotoxicity and improve CAR T-cell expansion and persistence, Dr. Jabbour said, noting that pooled efficacy and safety results from the FELIX phase 1b and 2 trials of heavily pretreated patients have previously been reported.
The findings support the use of obe-cel as a standard treatment in this patient population, and demonstrate that ongoing CAR T-cell persistence and B-cell aplasia are associated with improved EFS — without further consolidation therapy after treatment, he concluded.
This study was funded by Autolus Therapeutics. Dr. Jabbour disclosed ties with Abbvie, Ascentage Pharma, Adaptive Biotechnologies, Amgen, Astellas Pharma, Bristol-Myers Squibb, Genentech, Incyte, Pfizer, and Takeda.
These findings also highlight the favorable impact of CAR T persistence on treatment outcomes, and suggest that consolidative stem cell transplant (SCT) in R/R B-ALL patients treated with obe-cel does not improve outcomes, Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center, Houston, reported at the American Society of Clinical Oncology (ASCO) annual meeting.
The overall complete remission or complete remission with incomplete count recovery rate was 78% among 127 patients enrolled in the open-label, single-arm study and infused with obe-cel. Among the 99 patients who responded, 18 proceeded to consolidative SCT while in remission, Dr. Jabbour said, noting that all 18 who received SCT were in minimal residual disease (MRD)–negative remission at the time of transplant.
Of those 18 patients, 10 had ongoing CAR T persistence prior to transplant, he said.
At median follow-up of 21.5 months, 40% of responders were in ongoing remission without the need for subsequent consolidation with SCT or other therapy, whereas SCT did not appear to improve outcomes.
The median event-free survival (EFS) after censoring for transplant was 11.9 months, and the 12-month EFS rate was 49.5%. Without censoring for transplant, the EFS and 12-month EFS rate were 9.0 months and 44%, respectively.
“I would like to highlight that the time to transplant was 100 days, and of those 18 patients, all in MRD-negative status ... 80% relapsed or died from transplant-related complications,” Dr. Jabbour said.
Median overall survival (OS) without censoring for transplant was 15.6 months, and the 12-month OS rate was 61.1%. After censoring for transplant, the median OS and 12-month OS rate 23.8 months 63.7%, respectively. The survival curves were fully overlapping, indicating that transplant did not improve OS outcomes.
“Furthermore, when you look at the EFS and [OS], both show a potential plateau for a long-term outcome, and this trend is similar to what was reported in a phase 1 trial with 2 years of follow up and more,” Dr. Jabbour said.
The investigators also assessed the impact of loss of CAR T-cell persistence and loss of B-cell aplasia and found that “both ongoing CAR T-cell persistence and ongoing B-cell aplasia, were correlated with better event-free survival,” he noted, explaining that the risk of relapse was 2.7 times greater in those who lost versus maintained CAR T-cell persistence, and 1.7 times greater in those who lost versus maintained B-cell aplasia.
Among those with ongoing remission at 6 months, median EFS was 15.1 months in those who lost CAR T-cell persistence, whereas the median EFS was not reached in those who maintained CAR T-cell persistence.
Obe-cel is an autologous CAR T-cell product with a fast off-rate CD19 binder designed to mitigate immunotoxicity and improve CAR T-cell expansion and persistence, Dr. Jabbour said, noting that pooled efficacy and safety results from the FELIX phase 1b and 2 trials of heavily pretreated patients have previously been reported.
The findings support the use of obe-cel as a standard treatment in this patient population, and demonstrate that ongoing CAR T-cell persistence and B-cell aplasia are associated with improved EFS — without further consolidation therapy after treatment, he concluded.
This study was funded by Autolus Therapeutics. Dr. Jabbour disclosed ties with Abbvie, Ascentage Pharma, Adaptive Biotechnologies, Amgen, Astellas Pharma, Bristol-Myers Squibb, Genentech, Incyte, Pfizer, and Takeda.
FROM ASCO 2024